PURPOSE
This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).
METHODS
We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.
RESULTS
Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.
CONCLUSION
The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.
INTRODUCTION
Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related deaths.1-4 Even with potentially curative surgery, the 5-year survival rate is approximately 20%.2,5 Recent clinical trials in the adjuvant setting established survival benefits of gemcitabine + capecitabine and modified leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, oxaliplatin (FOLFIRINOX) over gemcitabine monotherapy in patients who initially presented with PDAC.6,7 Therefore, gemcitabine + capecitabine and modified FOLFIRINOX are preferred category 1 recommendations for resected PDAC according to National Comprehensive Cancer Network Guidelines.8
CONTEXT
Key Objective
Pancreatic ductal adenocarcinoma has a poor prognosis even after surgical resection. This phase III study compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with gemcitabine in patients with surgically resected pancreatic ductal adenocarcinoma.
Knowledge Generated
The primary end point of independently assessed disease-free survival was not met. However, overall survival favored nab-paclitaxel + gemcitabine versus gemcitabine (41.8 v 37.7 months) in the 5-year follow-up analysis.
Relevance (G.K. Schwartz)
-
This negative randomized phase III study fails to change the standard of care for patients with resected pancreatic cancer. Five-year overall survival data from this study suggest the use of nab-paclitaxel + gemcitabine as a treatment alternative for selected patients who cannot receive modified FOLFIRNOX.*
*Relevance section written by JCO Associate Editor Gary K. Schwartz, MD.
The phase III MPACT trial demonstrated superiority of first-line nab-paclitaxel + gemcitabine versus gemcitabine monotherapy in metastatic PDAC.9,10 The most common grade ≥ 3 adverse events (AEs) were neutropenia, leukopenia, fatigue, and peripheral neuropathy. Nab-paclitaxel + gemcitabine was hypothesized to extend disease-free survival (DFS) beyond the former gemcitabine standard in the adjuvant setting. The phase III APACT trial investigated efficacy and safety of adjuvant nab-paclitaxel + gemcitabine compared with those of gemcitabine in patients who had undergone surgical resection for PDAC.
METHODS
Study Oversight
Steering committee members (Data Supplement, online only) and the sponsor designed this trial. Data were collected by investigators and analyzed by a sponsor-employed statistician. All aspects of the study were monitored by the sponsor.
Patients
Patients were age ≥ 18 years, with histologically confirmed ductal PDAC with macroscopic complete resection, an Eastern Cooperative Oncology Group performance status ≤ 1, and no history of metastatic or locally recurrent disease. Patients were required to have serum carbohydrate antigen 19-9 < 100 U/mL and no recurrent disease (per computed tomography or magnetic resonance imaging scans) at screening (≤ 14 days of random assignment). Patients received no prior therapy (neoadjuvant, radiation, or systemic therapy) for PDAC. Patients were required to initiate adjuvant therapy ≤ 12 weeks of surgery (complete eligibility criteria, Data Supplement).
Study Design
APACT was a phase III, multicenter, open-label, randomized study conducted at 160 sites across 21 countries (EudraCT 2013-003398-91; ClinicalTrials.gov identifier: NCT01964430). Using a permuted-block random assignment method and interactive response technology, patients were randomly assigned 1:1 to receive nab-paclitaxel + gemcitabine or gemcitabine and stratified on the basis of resection status (R0 [tumor-free margin] v R1 [microscopically positive margin]), nodal status (lymph node–positive v lymph node–negative), and region (non-Asian regions [North America, Europe, and Australia] v Asia; a full list of countries, site names, and investigators can be found in Appendix Table A1 [online only]).
The Protocol (online only) and informed consent forms were approved by each study site's independent ethics committee or institutional review board before study initiation. This study was conducted in accordance with Good Clinical Practice, as denoted in the International Council for Harmonisation E6 requirements, and with the ethical principles outlined in the Declaration of Helsinki. Written informed consent was obtained before any study-related procedure.
Treatment
Patients received nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 or gemcitabine 1,000 mg/m2 alone as one intravenous infusion over 30-40 minutes on days 1, 8, and 15 of every 28-day cycle. Patients received six treatment cycles unless there was radiologic evidence of disease recurrence and unacceptable toxicity on the basis of the expert clinical judgment of the investigators or patient/physician decision otherwise. Supportive care could be administered per investigator's discretion. Two levels of dose modifications were permitted (Data Supplement).
End Points and Assessments
The primary end point, independently assessed DFS, was defined as time from random assignment to disease recurrence or death. DFS values were not censored by the cause of death, so it is possible that not all deaths were due to PDAC. Independently assessed DFS was determined by radiologists blinded to the treatment assignment. Independent reviewers assessed disease recurrence on the basis of radiologic review (computed tomography or magnetic resonance imaging). Evaluation of new lesions followed RECIST version 1.1. After random assignment, disease recurrence was assessed every 8 weeks for the first 24 weeks and then every 12 weeks for the next 2.5 years until 3 years after random assignment. After 3 years, disease recurrence was assessed every 24 weeks up to 5.5 years after random assignment.
Secondary end points were overall survival (OS) and safety. AEs were coded using Medical Dictionary for Regulatory Activities v21.0 and graded for intensity according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Investigators determined potential relationships between AEs and study treatments. Serious AEs were reported to the study sponsor's safety monitoring division.
Investigator-assessed DFS was evaluated in a prespecified sensitivity analysis; investigators determined recurrence using all available clinical information collected and evaluated using their expert judgment during the usual treatment of their patients. Independent review was not performed in real time or used to confirm investigator assessments (censoring rules provided in the Data Supplement). All patients were followed for survival. Initiation and types of new anticancer therapies were collected. Clinical assessments were made on days 1, 8, and 15 of each cycle (Data Supplement).
Statistical Analyses
Original assumptions about DFS were based on historical outcomes of investigator-assessed median DFS with adjuvant gemcitabine (range, 13.4-14.3 months).11,12 Contemporaneous phase III studies reported investigator-assessed median DFS with adjuvant gemcitabine ranging from 11.4 to 13.1 months.6,7,13 On the basis of an independent assessment, to achieve the median DFS of 13.5 months (gemcitabine) and 18.5 months (nab-paclitaxel + gemcitabine; equivalent to a hazard ratio [HR], 0.73), approximately 438 DFS events were required to allow 90% power to detect a 27% reduction of risk in disease recurrence or death at a two-sided significance threshold of .05.
All efficacy analyses were conducted in the intent-to-treat population. Distribution of DFS was estimated using the Kaplan-Meier method; medians and two-sided 95% CIs were provided. DFS was compared between arms using the stratified log-rank test, with stratification factors of resection and lymph node status. The associated HR and two-sided 95% CI were provided using the stratified Cox proportional hazards model. The same analyses were used for OS and investigator-assessed DFS. Percentage of protocol dose was calculated as percentage of dose intensity/protocol-specified weekly dose. All P values are descriptive and were not adjusted for multiplicity.
Concordance between independent and investigator review of disease recurrence was summarized. Patient data were censored in the independent review after the start of a new anticancer therapy or cancer-related surgery. Therefore, new lesions appearing afterward were not counted as recurrence. All statistical analyses were conducted using SAS v9.2 (SAS Institute, Cary, NC) or higher (Data Supplement).
RESULTS
Patients
One thousand two hundred twenty-six patients were screened, and 866 (71%) were enrolled between April 2014 and April 2016 in Europe (47%), North America (35%), Asia (12%), and Australia (6%), and randomly assigned to receive nab-paclitaxel + gemcitabine (n = 432) or gemcitabine (n = 434, Fig 1). Reasons for screen failure are given in the Data Supplement.
FIG 1.
CONSORT diagram. Flow diagram results between treatment arms after primary data cutoff (December 31, 2018). aCompleted indicates patients who finished all six treatment cycles and received ≥ 2 doses of the study medication during cycle 6. AE, adverse event; Gem, gemcitabine; ITT, intent-to-treat; nab-P, nab-paclitaxel.
Demographic and baseline characteristics were balanced between arms (Table 1). The median age of patients was 64.0 years (interquartile range [IQR], 57.0-70.0). Most patients were men (56%) and had an Eastern Cooperative Oncology Group performance status of 0 (60%), R0 resection (76%), and lymph node involvement (72%).
TABLE 1.
Demographic and Baseline Clinical Characteristics (intent-to-treat population)
All analyses were conducted using data collected at the primary data cutoff (December 31, 2018) except for OS analyses, which were conducted at the primary data cutoff, the 16-month follow-up analysis cutoff (April 3, 2020), and the 5-year follow-up analysis cutoff (April 9, 2021).
Treatment
One treatment cycle was defined as once-weekly administration of the study drug(s) for 3 weeks followed by 1 week without study treatment. In the treated population, six treatment cycles were administered to 69% (nab-paclitaxel + gemcitabine) and 75% (gemcitabine) of patients. The median treatment duration was 24 weeks in each arm (overall IQR, 20.1-24.3; Data Supplement). The median percentages of protocol dose that patients in the nab-paclitaxel + gemcitabine arm received were 75% (nab-paclitaxel) and 80% (gemcitabine) versus 91% with gemcitabine. In the nab-paclitaxel + gemcitabine arm, 64% of patients had ≥ 1 dose reduction; the corresponding rate in the gemcitabine arm was 50%. Dose omissions, delays, and intensity data are reported in the Data Supplement.
Efficacy
At primary data cutoff (December 31, 2018), the median follow-up was 38.5 (IQR, 33.8-43.0) months. For the primary end point of independently assessed DFS, 439 of all treated patients (51%) had progressed or died. The median independently assessed DFS was 19.4 months (95% CI, 16.62 to 21.91) with nab-paclitaxel + gemcitabine versus 18.8 months (95% CI, 13.83 to 20.30) with gemcitabine. The difference between arms was not statistically significant (HR, 0.88; 95% CI, 0.729 to 1.063; P = .18; Fig 2A).
FIG 2.
Kaplan-Meier curves of DFS and OS. Kaplan-Meier curves of DFS by (A) independent assessment and (B) investigator assessment (primary data cutoff, December 31, 2018). OS at data cutoffs of the (C) primary analysis, (D) 16-month follow-up (April 3, 2020), and (E) 5-year follow-up (April 9, 2021). OS rates for ≥ 5 years were 38% with nab-paclitaxel + Gem and 31% with Gem. DFS, disease-free survival; Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; OS, overall survival.
For investigator-assessed DFS, 571 of all treated patients (66%) had experienced disease progression or died. The median investigator-assessed DFS was 16.6 months (95% CI, 14.55 to 19.29) with nab-paclitaxel + gemcitabine versus 13.7 months (95% CI, 11.24 to 16.00) with gemcitabine (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02; Fig 2B). The concordance between independent and investigator-assessed DFS was 77% (nab-paclitaxel + gemcitabine, 78%; gemcitabine, 76%). A summary of censoring is provided in the Data Supplement. Patients with recurrence per investigator assessment who started subsequent therapy (n = 26 [nab-paclitaxel + gemcitabine] and n = 31 [gemcitabine]) were censored for the independently assessed DFS analysis at initiation of subsequent anticancer therapy.
OS data at the primary data cutoff were 68% mature (427 of 630 target events); 48% (nab-paclitaxel + gemcitabine) and 51% (gemcitabine) of patients had died. The median OS was 40.5 months (IQR, 20.7 to not estimable) with nab-paclitaxel + gemcitabine compared with 36.2 (IQR, 17.7-53.3) months with gemcitabine (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045; Fig 2C).
A 16-month follow-up OS analysis was conducted (cutoff, April 3, 2020; median follow-up for survival, 51.4 [IQR, 47.0-57.0] months) on the basis of 511 events (81% mature); for nab-paclitaxel + gemcitabine versus gemcitabine, 57% versus 61% of patients had died. The median OS was 41.8 months (95% CI, 35.55 to 47.28) with nab-paclitaxel + gemcitabine versus 37.7 months (95% CI, 31.11 to 40.51) with gemcitabine (HR, 0.82; 95% CI, 0.687 to 0.973; P = .023; Fig 2D).
A 5-year follow-up OS analysis was also conducted. At the cutoff (April 9, 2021), patients had been followed for ≥ 5 years or discontinued from the study. The overall median follow-up for OS was 63.2 (IQR, 60.1-68.7) months. A total of 268 and 287 events occurred in the nab-paclitaxel + gemcitabine and gemcitabine arms, respectively (88% mature); 62% versus 66% of patients had died. The median OS with nab-paclitaxel + gemcitabine was 41.8 months compared with 37.7 months with gemcitabine (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091; Fig 2E). At a 5-year follow-up, the estimates of OS rates for ≥ 5 years were 38% with nab-paclitaxel + gemcitabine and 31% with gemcitabine.
Subsequent Therapy
Overall, 55% (nab-paclitaxel + gemcitabine) and 56% (gemcitabine) of patients received a subsequent new anticancer therapy or cancer-related surgery (Data Supplement). Fluorouracil-based regimens (fluoropyrimidine monotherapy or a non-FOLFIRINOX combination; 26% [nab-paclitaxel + gemcitabine] versus 24% [gemcitabine]) and FOLFIRINOX (21% v 18%) were most common. Eight percent of patients in the nab-paclitaxel + gemcitabine group and 21% in the gemcitabine arm received a new nab-paclitaxel–based subsequent therapy.
Subgroup Efficacy Analyses
Results of the primary end point of independently assessed DFS in the primary analyses for prespecified subgroups are presented in Figure 3A. Subgroup analyses of investigator-assessed DFS and OS were also performed (primary data cutoff, Data Supplement and Fig 3B; 5-year follow-up data cutoff [OS only], Data Supplement). Patterns of independently assessed DFS (Fig 3A) and OS (Fig 3B) in the subgroups were generally consistent with observations from the intent-to-treat population.
FIG 3.
Forest plot subgroup analysis of DFS and OS. At the primary data cutoff (December 31, 2018), prespecified (A) blinded, independent, centrally reviewed DFS and (B) OS. CA19-9, carbohydrate antigen 19-9; DFS, disease-free survival; ECOG PS, Eastern Cooperative Oncology Group performance status, Gem, gemcitabine; HR, hazard ratio; LN, lymph node; nab-P, nab-paclitaxel; OS, overall survival; ULN, upper limit of normal; WNL, within normal limits.
Safety
Treatment-emergent adverse event (TEAE) data reported herein are from the primary analysis (cutoff, December 31, 2018). All treated patients in the nab-paclitaxel + gemcitabine arm and 99% of those in the gemcitabine arm had ≥ 1 TEAE; grade ≥ 3 TEAEs were reported in 86% and 68% of patients, respectively (Table 2). At least one serious TEAE occurred in 41% and 23% of patients, respectively. In the nab-paclitaxel + gemcitabine arm, 27% (nab-paclitaxel) and 17% (gemcitabine) of patients discontinued treatment because of TEAEs versus 10% in the gemcitabine arm. Two patients (< 1%) died in each arm because of TEAEs (nab-paclitaxel + gemcitabine arm: pneumonia and sepsis [n = 1 patient each]; gemcitabine arm: drug-induced liver injury and hepatic failure [n = 1] and capillary leak syndrome [n = 1]).
TABLE 2.
Safety (treated population)
The most frequent grade ≥ 3 TEAEs with nab-paclitaxel + gemcitabine versus gemcitabine were neutropenia (49% v 43%), anemia (15% v 8%), and fatigue (10% v 3%). The incidence of grade ≥ 3 peripheral neuropathy was 15% (nab-paclitaxel + gemcitabine) versus 0% (gemcitabine). Among patients who experienced grade ≥ 3 peripheral neuropathy, 17% improved by ≥ 1 grade in a median of 195.0 days, whereas 16% improved to grade 1 or experienced resolution of peripheral neuropathy (median time to improvement, not reached). Of 77 treatment-emergent occurrences of grade ≥ 3 peripheral neuropathy observed among 64 patients, the majority (62%) commenced during cycle 4 or later. At the primary analysis cutoff, 61% of all grade ≥ 3 peripheral neuropathy TEAEs were resolved. Additional grade ≥ 3 TEAEs of special interest included gastrointestinal events (10% v 2%), hepatic toxicity (6%, both arms), sepsis (5% v 2%), and febrile neutropenia (5% v 1%). White blood cell growth factor support was received by 153 (35%; nab-paclitaxel + gemcitabine) and 91 (21%; gemcitabine) patients.
DISCUSSION
The APACT trial did not meet the primary end point of independently assessed DFS. The prespecified sensitivity analysis of investigator-assessed DFS and the OS data suggested improved outcomes with nab-paclitaxel + gemcitabine versus gemcitabine; however, since the primary end point was not met, comparisons are considered descriptive. The safety profile with adjuvant nab-paclitaxel + gemcitabine was generally consistent with data reported previously.9 To our knowledge, APACT was the first trial of adjuvant treatment of PDAC to use blinded, centrally reviewed, independently assessed DFS as the primary end point, which was selected on the basis of an assumption that it would increase the scientific rigor of the trial and reduce possible unintentional investigator bias on survival outcomes. However, APACT was powered on the basis of investigator-assessed DFS data. This study offers a clinically important lesson for the field as radiographic postsurgical changes are sometimes difficult to distinguish from local recurrence.
A moderate concordance was observed between assessments of DFS. The discrepancy between the DFS analyses was likely due to the greater proportion of patients censored by independent assessments (48% [nab-paclitaxel + gemcitabine] and 51% [gemcitabine]) versus investigator assessments (35% [nab-paclitaxel + gemcitabine] and 33% [gemcitabine]) and the subsequent difference in number of DFS events (439 v 571 events, respectively). Per the investigator assessment, some patients were considered to have progressive disease and subsequent therapy was initiated. However, patients might not have met the formal radiologic criteria for progression; thus, their data were censored for central review at the time of initiation of subsequent therapy. Among patients who received gemcitabine monotherapy in APACT, the independently assessed median DFS (18.8 months) was longer than the investigator-assessed DFS (13.7 months), a discrepancy similar to those with investigator assessments in the gemcitabine arms of previous trials, including ESPAC-4 (13.4 months) and PRODIGE-24 (12.8 months).6,7,11-13 The results presented reflect complexities of accurately defining the recurrence time point. In addition, radiologic review in the absence of clinical context may be suboptimal for recurrence detection in resected PDAC, which represents a limitation of this study and could be considered in future trial designs in the adjuvant setting. Our findings suggest that radiologic data should be supported by clinical assessments (symptomatic deterioration, carbohydrate antigen 19-9 levels, pathology, and second-level diagnostic imaging such as positron-emission tomography). Furthermore, certain areas of recurrence, such as in the surgical bed and mesenteric nodes, can be difficult to diagnose by imaging alone. These interpretations are consistent with an analysis of multiple ovarian cancer trials with similarly conflicting results.14 Possible variations in the determination of resection status of patients represent a limitation in this study. Since APACT enrolled patients globally, there was no central pathology review and there might have been regional differences in standards for defining R0 versus R1.
After the initiation of APACT, capecitabine + gemcitabine and modified FOLFIRINOX became category 1–preferred regimens according to National Comprehensive Cancer Network Guidelines.8 In the 16-month follow-up analysis, treatment with nab-paclitaxel + gemcitabine resulted in an effect on OS in APACT (HR, 0.82) similar to capecitabine + gemcitabine in ESPAC-4 (HR, 0.82)6 and a numerically higher 5-year survival rate (36% with nab-paclitaxel + gemcitabine in APACT and 28% with gemcitabine-capecitabine in ESPAC-415); however, these observations are not comparable because of differences in patient selection and subsequent therapy. Interestingly, the secondary end point of the phase II SWOG S1505 trial of perioperative nab-paclitaxel + gemcitabine versus modified FOLFIRINOX revealed a greater complete or major pathologic response rate and numerically longer DFS with nab-paclitaxel + gemcitabine specifically in patients undergoing resection.16 Additional phase II data have suggested activity of perioperative nab-paclitaxel + gemcitabine.17-19 Future studies investigating the impact of metastatic disease on patient response may elucidate the difference seen in DFS and OS.
The safety profile with adjuvant nab-paclitaxel + gemcitabine was generally consistent with that established by the phase III MPACT trial and revealed no unexpected AEs; however, some exceptions were noted. In both arms, grade ≥ 3 neutropenia was more frequent (49% with nab-paclitaxel + gemcitabine; 43% with gemcitabine) than in MPACT (38% with nab-paclitaxel + gemcitabine; 27% with gemcitabine). Although the 15% incidence of grade ≥ 3 peripheral neuropathy reported here was consistent with MPACT (17%), peripheral neuropathy in most patients in APACT (84% of those who experienced grade ≥ 3 peripheral neuropathy) had not improved to grade ≤ 1 as of the data cutoff for the primary analysis, an unexpected finding. However, 61% of all grade ≥ 3 peripheral neuropathy events were resolved at the time of the primary analysis. Incidences of grade ≥ 3 leukopenia, thrombocytopenia, and fatigue in the nab-paclitaxel + gemcitabine arm were numerically lower than what was observed in MPACT.9 The qualitative differences in safety outcomes may be the greater treatment exposure and duration of taxane-based therapy in APACT compared with the metastatic setting in MPACT. The median duration of treatment in both the nab-paclitaxel + gemcitabine and gemcitabine groups was 24 weeks (approximately 6 months in both groups), whereas the median duration of treatment in the MPACT trial was 3.9 months in the nab-paclitaxel + gemcitabine group and 2.8 months in the gemcitabine group.9 The median percentage of protocol doses of gemcitabine was 80% (nab-paclitaxel + gemcitabine arm) versus 91% (gemcitabine arm); despite the nab-paclitaxel + gemcitabine arm receiving fewer doses of gemcitabine, the investigator-assessed DFS and the OS data still supported improved outcomes with nab-paclitaxel + gemcitabine versus gemcitabine. This leaves two possible explanations: (1) the 11% difference had a negligible impact on outcomes and (2) the addition of nab-paclitaxel to gemcitabine might have compensated for any potential loss in efficacy from the 11% lower dose of gemcitabine in the combination arm.
The trial did not meet the primary end point; nonetheless, the median OS results in the 5-year follow-up analysis (April 9, 2021; 41.8 v 37.7 months [nab-paclitaxel + gemcitabine v gemcitabine, respectively]) provide valuable data pertinent to outcomes with adjuvant therapy in resected PDAC. Secondary analyses suggest that this regimen may provide insight when defining end points for future studies. Collectively, the data reflect the challenges of independent radiologic review without additional pertinent clinical data in this setting, particularly in a patient population highly selected for early-stage disease. Furthermore, nab-paclitaxel + gemcitabine represents an available treatment option for patients who cannot or prefer not to receive modified FOLFIRINOX or gemcitabine + capecitabine. Future analyses of the final OS, quality of life, and biomarker data may further inform management of patients with resected PDAC, particularly regarding the role of nab-paclitaxel + gemcitabine.
ACKNOWLEDGMENT
The authors thank the patients who participated in the study and their family members as well as the investigators and staff who conducted the study. Study and data management were provided by Heidi Marks, Yessenia Cruz-Garcia, Jacqui Farnell, and Wendy Garwood. Biostatistics assistance was provided by Olivia Tian and Juan Shen. The authors are fully responsible for all content and editorial decisions for this manuscript. M.L., S.F., Y.L.B., and B.L. are not currently employed at Bristol Myers Squibb. A list of APACT investigators and sites can be found in Appendix Table A1.
APPENDIX
TABLE A1.
List of APACT Investigators and Sites
Margaret A. Tempero
Honoraria: Novartis, CPRIT, Bluestar Genomics
Consulting or Advisory Role: Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Ipsen, Swedish Orphan Biovitrum, Karyopharm Therapeutics, Merck, Astellas Pharma, BeiGene, Biomea Fusion, BioSapien, Bluestar Genomics, Cend Therapeutics Inc, Debiopharm Group, Geistlich Pharma, Global Bio Access Fund, Jazz Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals UK Ltd, ONCOLYTICS, Steba Biotech
Research Funding: Celgene, Halozyme, Bristol Myers Squibb/Ono Pharmaceutical, Pharmacyclics
Travel, Accommodations, Expenses: BIOPHARM, Bristol Myers Squibb, Pharmacyclics, PharmaCyte Biotech, AbbVie, GlaxoSmithKline, Merck
Eileen M. O'Reilly
Consulting or Advisory Role: Adicet Bio (I), AstraZeneca, Alnylam (I), Autem Medical (I), BeiGene (I), Berry Genomics (I), CytomX Therapeutics, Eisai (I), Exelixis (I), Genentech/Roche (I), Genoscience Pharma (I), Helio Health (I), Incyte (I), Ipsen, Legend Biotech (I), Merck, Nerviano Medical Sciences (I), QED Therapeutics (I), RedHill Biopharma (I), Yiviva (I), Novartis, Rafael Pharmaceuticals, CytomX Therapeutics, Seattle Genetics, Boehringer Ingelheim, IDEAYA Biosciences, Noxxon Pharma, BioSapien, Thetis Pharma, BioSapien, Cend Therapeutics, Flatiron Health (I)
Research Funding: AstraZeneca/MedImmune (Inst), Celgene (Inst), Genentech (Inst), Roche (Inst), Silenseed (Inst), Arcus Ventures (Inst), BioNTech (Inst), Elicio Therapeutics (Inst), Parker Institute for Cancer Immunotherapy (Inst)
Uncompensated Relationships: Thetis Pharma
Do-Youn Oh
Consulting or Advisory Role: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Halozyme, Zymeworks, Celgene, Basilea, BeiGene, Turning Point Therapeutics, Yuhan, Arcus Biosciences, IQVIA
Research Funding: AstraZeneca, Novartis, Array BioPharma, Lilly, Servier, BeiGene, MSD, Handok
Giampaolo Tortora
Consulting or Advisory Role: Celgene, Merck Serono, MSD Oncology, Bristol Myers Squibb/Celgene, AstraZeneca, Dompé Farmaceutici
Travel, Accommodations, Expenses: Merck Serono, Roche
Heung-Moon Chang
Research Funding: Taiho Oncology (Inst), Celgene (Inst), Zymeworks (Inst), Astellas Pharma (Inst)
Charles D. Lopez
Research Funding: Taiho Pharmaceutical, Roche/Genentech (Inst)
Tanios Bekaii-Saab
Consulting or Advisory Role: Amgen (Inst), Ipsen (Inst), Lilly (Inst), Bayer (Inst), Roche/Genentech (Inst), AbbVie, Incyte (Inst), Immuneering, Seattle Genetics (Inst), Pfizer (Inst), Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine, Arcus Biosciences (Inst), Stemline Therapeutics, Kanaph Therapeutics, Deciphera, Illumina, Foundation Medicine
Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent WO/2019/055687
Other Relationship: Exelixis, Merck (Inst), AstraZeneca, Lilly, Pancreatic Cancer Action Network, FibroGen, Suzhou Kintor Pharmaceuticals, 1Globe Health Institute, Imugene, Xilis, Replimune, Sun Biopharma, UpToDate
Open Payments Link: https://openpaymentsdata.cms.gov/physician/636276
Andrew H. Ko
Honoraria: Research to Practice, Clinical Care Options, Medscape, BioAscent, MJH Life Sciences, Gerson Lehrman Group
Consulting or Advisory Role: ERYTECH Pharma, Imugene, SynCoreBio, Roche/Genentech, Ipsen, Five Prime Therapeutics, Tyme, Turning Point Therapeutics, Signatera, Syros Pharmaceuticals
Speakers' Bureau: Clinical Care Options
Research Funding: Celgene (Inst), Merck (Inst), Genentech/Roche (Inst), Bristol Myers Squibb (Inst), AbGenomics International (Inst), Apexigen (Inst), Astellas Pharma (Inst), Leap Therapeutics (Inst), BioMed Valley Discoveries (Inst), CrystalGenomics (Inst)
Armando Santoro
Consulting or Advisory Role: Bristol Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ARQULE, Incyte
Speakers' Bureau: Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, BMS, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD
Joon Oh Park
Consulting or Advisory Role: Celgene, Merck Serono, Servier, AstraZeneca, MediRama
Research Funding: Celgene, MedPacto, Servier, ABL Bio, Eutilex
Marcus S. Noel
Consulting or Advisory Role: Celgene, Taiho Pharmaceutical, Ipsen
Speakers' Bureau: Taiho Pharmaceutical, Celgene, Daiichi Sankyo/Astra Zeneca
Andrew Dean
Stock and Other Ownership Interests: A2A Pharmaceuticals
Honoraria: Amgen
Travel, Accommodations, Expenses: Novartis, Juniper Biologics
Uncompensated Relationships: A2A Pharmaceuticals
Hanno Riess
Leadership: Bayer, BMS GmbH & Co KG, Mylan, Boehringer Ingelheim
Speakers' Bureau: Bayer, BMS GmbH & Co KG
Eric Van Cutsem
Consulting or Advisory Role: Bayer, Lilly, Roche, Servier, Bristol Myers Squibb, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Array BioPharma, Daiichi Sankyo, Pierre Fabre, Taiho Pharmaceutical, Incyte, Astellas Pharma, GlaxoSmithKline, Nordic Group, Pfizer, Takeda, ALX Oncology, AbbVie, BeiGene, Boehringer Ingelheim, Mirati Therapeutics, Seattle Genetics, TERUMO, Zymeworks, Ipsen
Research Funding: Amgen (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Novartis (Inst), Roche (Inst), Ipsen (Inst), Merck (Inst), Merck KGaA (Inst), Servier (Inst), Bristol Myers Squibb (Inst)
Jordan Berlin
Consulting or Advisory Role: Bayer Health, QED Therapeutics, Ipsen, Mirati Therapeutics, Insmed, Oxford BioTherapeutics, Merck KGaA, BioSapien
Research Funding: Bayer (Inst), Incyte (Inst), Karyopharm Therapeutics (Inst), EMD Serono (Inst), Boston Biomedical (Inst), PsiOxus Therapeutics (Inst), Pfizer (Inst), Lilly (Inst), Dragonfly Therapeutics (Inst), AbbVie (Inst), I-MAB (Inst), Astellas Pharma (Inst), Atreca (Inst), Day One Biopharmaceuticals (Inst), Bristol Myers Squibb/Celgene (Inst), Sumitomo Dainippon Pharma Oncology (Inst), 23andMe (Inst), Totus Medicines (Inst), Tyra Biosciences (Inst)
Other Relationship: Novocure, Pancreatic Cancer Action Network, Karyopharm Therapeutics, AstraZeneca
Philip Philip
Honoraria: Celgene, Bayer, Ipsen, Merck, AstraZeneca, TriSalus Life Sciences, Blueprint Medicines, SynCoreBio, Incyte, Bristol Myers Squibb/Medarex, Guardant Health, Rafael Pharmaceuticals, Daiichi Sankyo/Astra Zeneca
Consulting or Advisory Role: Celgene, Ipsen, Merck, TriSalus Life Sciences, Daiichi Sankyo, SynCoreBio, Taiho Pharmaceutical
Speakers' Bureau: Celgene, Bayer, Ipsen, Novartis, Incyte, Bristol Myers Squibb/Medarex
Research Funding: Bayer (Inst), Incyte (Inst), Karyopharm Therapeutics (Inst), Merck (Inst), Taiho Pharmaceutical (Inst), Momenta Pharmaceuticals (Inst), Novartis (Inst), Plexxikon (Inst), Immunomedics (Inst), Regeneron (Inst), Genentech (Inst), TYME (Inst), Caris Life Sciences (Inst), ASLAN Pharmaceuticals (Inst), QED Therapeutics (Inst), Halozyme (Inst), Boston Biomedical (Inst), Advanced Accelerator Applications (Inst), Lilly (Inst), Merus (Inst)
Travel, Accommodations, Expenses: Rafael Pharmaceuticals, Celgene, AbbVie
Uncompensated Relationships: Rafael Pharmaceuticals, Caris MPI
David Goldstein
Honoraria: Sun Biopharma, Boehringer Ingelheim, AstraZeneca
Consulting or Advisory Role: Sun Biopharma, Seattle Genetics, AstraZeneca, Boehringer Ingelheim
Research Funding: Amgen (Inst), Pfizer (Inst), Celgene (Inst), Bayer (Inst), Zucero Therapeutics (Inst), Bristol Myers Squibb (Inst)
Josep Tabernero
Stock and Other Ownership Interests: Oniria Therapeutics
Consulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann LaRoche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, NeoPhore, Orion Biotechnology, Hutchison MediPharma, Scandion Oncology, Ona Therapeutics, SOTIO, Inspirna, Scorpion Therapeutics
Other Relationship: Medscape, MJH Life Sciences, PeerView, Physicians' Education Resource, Imedex/HMP
Mingyu Li
Employment: Ascentage Pharma
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene, Ascentage Pharma
Stefano Ferrara
Employment: SOTIO, BeiGene AG, Bristol Myers Squibb/Celgene/Juno (I)
Stock and Other Ownership Interests: BeiGene
George Zhang
Employment: Bristol Myers Squibb/Celgene
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene
Brian Lu
Employment: Bristol Myers Squibb/Celgene
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene
Andrew V. Biankin
Employment: AstraZeneca/MedImmune, BMSi
Leadership: Cambridge Cancer Genomics, Concr, Wollemia Oncology, Gabriel Precision Oncology, Cumulus Oncology
Stock and Other Ownership Interests: Cumulus Oncology, Modulus Oncology, Wollemia Oncology, Concur, Cambridge Cancer Genomics, Gabriel Precision Oncology, Humans.ai
Honoraria: Havas Lynx Group
Consulting or Advisory Role: AstraZeneca/MedImmune
Speakers' Bureau: Celgene
Research Funding: Celgene (Inst), AstraZeneca/MedImmune (Inst)
Patents, Royalties, Other Intellectual Property: Agilent Technologies—Royalty payments to Institute (University of Glasgow)
Michele Reni
Consulting or Advisory Role: Celgene, Lilly, AstraZeneca, Panavance Therapeutics, Viatris, SOTIO, Servier, MSD/AstraZeneca
Research Funding: Celgene (Inst), AstraZeneca (Inst)
Travel, Accommodations, Expenses: Celgene
Other Relationship: Celgene, AstraZeneca
No other potential conflicts of interest were reported.
PRIOR PRESENTATION
Presented at AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care 2019, Boston, MA, September 5-9, 2019; American Pancreatic Association 2019, Maui, HI, November 6-9, 2019; ASCO 2019, Chicago, IL, June 1-3, 2019; European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2019, Barcelona, Spain, July 3-6, 2019; ASCO 2020, virtual, May 29-31, 2020; ASCO Gastrointestinal Cancers Symposium 2020, San Francisco, CA, January 23-25, 2020; European Society for Medical Oncology Asia Congress 2020, virtual; November 20-22, 2020; and World Congress on Gastrointestinal Cancer 2021, virtual, June 20-July 3, 2021.
SUPPORT
Supported by Bristol Myers Squibb and by Celgene, a Bristol Myers Squibb Company, Princeton, NJ. Professional medical writing and editorial assistance was provided by Narender Dhingra, MBBS, PhD, CMPP, of Meditech Media, Ltd; Aaron Runkle, PhD, CMPP, of Meditech Media, Ltd; and Krystin Tran, PharmD, of Chrysalis Medical Communications LLC and funded by Bristol Myers Squibb. Medical review was supported by Julie Jeanes, Emily Mantovani, Desmond McGovern, Alfredo Romano, David Eardley, and Lotus Yung.
CLINICAL TRIAL INFORMATION
Contributor Information
Collaborators: Richard Epstein, Paul Vasey, Jeremy Shapiro, Matthew Burge, Yu Jo Chua, Marion Harris, Nick Pavlakis, Niall Tebbutt, Gerald Prager, Christian Dittrich, Friedrich Längle, Kathrin Philipp-Abbrederis, Richard Greil, Herbert Stöger, Michael Girschikofsky, Thomas Kuehr, Jean-Luc Van Laethem, Stéphanie Laurent, Neesha Dhani, Yoo Joung Ko, Scot Dowden, Petr Kavan, Mustapha Édouard Tehfe, Eugen Kubala, Milan Kohoutek, Per Pfeiffer, Mette Yilmaz, Vibeke Parner, Tapio Salminen, Leena-Maija Soveri, Eija Korkeila, Pia Osterlund, Julien Taieb, David Tougeron, Pascal Artru, François Xavier Caroli-Bosc, Rosine Guimbaud, Antony Turpin, Thomas Walter, Jean Baptiste Bachet, Volker Kunzmann, Florian Kreth, Andreas Block, Marino Venerito, Helmut Oettle, Meinolf Karthaus, Jörg Trojan, Gunnar Folprecht, Markus Lerch, Frank Kullmann, Marcel Reiser, Volker Heinemann, Marcus-Alexander Wörns, Holger Schulz, Benjamin Garlipp, Thomas Yau, Lam Stephen Chan, Balazs Juhasz, László Landherr, Tamas Pinter, György Bodoky, Zsuzsanna Kahán, Raymond McDermott, Derek Power, Luca Gianni, Salvatore Siena, Michele Milella, Alfredo Falcone, Rossana Berardi, Cinzia Bagalà, Francesco Di Costanzo, Fausto Roila, Andrea Ardizzoni, Evaristo Maiello, Silvia Fanello, Johanna Wilmink, Jan Willem de Groot, Geert Creemers, Eduardo Barroso, Tânia Rodrigues, Cristina Sarmento, Cheng Ean Chee, David Tai, Teresa Macarulla Mercade, Manuel Hidalgo Medina, Alfredo Carrato Mena, Joan Maurel Santasusana, Maria Jose Flor Oncala, Carlos Gomez Martin, Rafael Lopez, Andres Muñoz, Ruth Vera Garcia, Inmaculada Ales, Berta Laquente Sáez, Fernando Rivera, Javier Sastre, Cheng-Chung Wu, Yu-Wen Tien, De-Chuan Chan, Tsann-Long Hwang, Jeffry Evans, Jonathan Wadsley, Pippa Corrie, Andrew Biankin, Andrew Ko, Dana Cardin, Elena Chiorean, Johanna Bendell, Anne Noonan, Hedy Kindler, Nishan Fernando, Muhammad Beg, Thomas George, Marcus Noel, Noelle LoConte, Francis Arena, James Posey, Rajat Malhotra, Charles Lopez, Davendra Sohal, Robert McWilliams, Warren Brenner, Mark Womack, Rahul Seth, Renuka lyer, Nathan Bahary, Robert Marsh, Robert Ramirez, Cynthia Chua, James Reeves, Gulam Manji, Anthony El-Khoueiry, Robert Weaver, Vaibhav Sahai, Wells Messersmith, Robert Dreicer, Ahmed Zakari, Andrea Bullock, Benjamin Musher, Mitesh Borad, Edward Kim, David Bajor, Tim Huyck, Hassan Hatoum, Henry Xiong, Boris Pasche, Jill Lacy, Olugbenga Olowokure, Allen Cohn, Donald Richards, Robert Martin, Andrew Paulson, Paul Fanta, Smitha Krishnamurthi, Paul Oberstein, and Jyotsna Fuloria
DATA SHARING STATEMENT
Data requests may be submitted to Celgene, a Bristol Myers Squibb Company, at https://vivli.org/ourmember/celgene/ and must include a description of the research proposal.
AUTHOR CONTRIBUTIONS
Conception and design: Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Chung-Pin Li, Giampaolo Tortora, Armando Santoro, Hanno Riess, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Yvan Le Bruchec, Brian Lu, Andrew V. Biankin, Michele Reni
Financial support: Brian Lu
Administrative support: Uwe Pelzer, Josep Tabernero, Stefano Ferrara, Andrew V. Biankin
Provision of study materials or patients: Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Joon Oh Park, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Eric Van Cutsem, Jordan Berlin, Philip Philip, Malcolm Moore, David Goldstein, Josep Tabernero, Andrew V. Biankin, Michele Reni
Collection and assembly of data: Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Heung-Moon Chang, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Joon Oh Park, Marcus S. Noel, Giovanni Luca Frassineti, Yan-Shen Shan, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Yvan Le Bruchec, Brian Lu, Michele Reni
Data analysis and interpretation: Margaret A. Tempero, Uwe Pelzer, Eileen M. O'Reilly, Jordan Winter, Do-Youn Oh, Chung-Pin Li, Giampaolo Tortora, Charles D. Lopez, Tanios Bekaii-Saab, Andrew H. Ko, Armando Santoro, Marcus S. Noel, Andrew Dean, Hanno Riess, Eric Van Cutsem, Jordan Berlin, Malcolm Moore, David Goldstein, Josep Tabernero, Mingyu Li, Stefano Ferrara, Yvan Le Bruchec, George Zhang, Brian Lu, Andrew V. Biankin, Michele Reni
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Margaret A. Tempero
Honoraria: Novartis, CPRIT, Bluestar Genomics
Consulting or Advisory Role: Bristol Myers Squibb, AbbVie, GlaxoSmithKline, Ipsen, Swedish Orphan Biovitrum, Karyopharm Therapeutics, Merck, Astellas Pharma, BeiGene, Biomea Fusion, BioSapien, Bluestar Genomics, Cend Therapeutics Inc, Debiopharm Group, Geistlich Pharma, Global Bio Access Fund, Jazz Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals UK Ltd, ONCOLYTICS, Steba Biotech
Research Funding: Celgene, Halozyme, Bristol Myers Squibb/Ono Pharmaceutical, Pharmacyclics
Travel, Accommodations, Expenses: BIOPHARM, Bristol Myers Squibb, Pharmacyclics, PharmaCyte Biotech, AbbVie, GlaxoSmithKline, Merck
Eileen M. O'Reilly
Consulting or Advisory Role: Adicet Bio (I), AstraZeneca, Alnylam (I), Autem Medical (I), BeiGene (I), Berry Genomics (I), CytomX Therapeutics, Eisai (I), Exelixis (I), Genentech/Roche (I), Genoscience Pharma (I), Helio Health (I), Incyte (I), Ipsen, Legend Biotech (I), Merck, Nerviano Medical Sciences (I), QED Therapeutics (I), RedHill Biopharma (I), Yiviva (I), Novartis, Rafael Pharmaceuticals, CytomX Therapeutics, Seattle Genetics, Boehringer Ingelheim, IDEAYA Biosciences, Noxxon Pharma, BioSapien, Thetis Pharma, BioSapien, Cend Therapeutics, Flatiron Health (I)
Research Funding: AstraZeneca/MedImmune (Inst), Celgene (Inst), Genentech (Inst), Roche (Inst), Silenseed (Inst), Arcus Ventures (Inst), BioNTech (Inst), Elicio Therapeutics (Inst), Parker Institute for Cancer Immunotherapy (Inst)
Uncompensated Relationships: Thetis Pharma
Do-Youn Oh
Consulting or Advisory Role: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho Pharmaceutical, ASLAN Pharmaceuticals, Halozyme, Zymeworks, Celgene, Basilea, BeiGene, Turning Point Therapeutics, Yuhan, Arcus Biosciences, IQVIA
Research Funding: AstraZeneca, Novartis, Array BioPharma, Lilly, Servier, BeiGene, MSD, Handok
Giampaolo Tortora
Consulting or Advisory Role: Celgene, Merck Serono, MSD Oncology, Bristol Myers Squibb/Celgene, AstraZeneca, Dompé Farmaceutici
Travel, Accommodations, Expenses: Merck Serono, Roche
Heung-Moon Chang
Research Funding: Taiho Oncology (Inst), Celgene (Inst), Zymeworks (Inst), Astellas Pharma (Inst)
Charles D. Lopez
Research Funding: Taiho Pharmaceutical, Roche/Genentech (Inst)
Tanios Bekaii-Saab
Consulting or Advisory Role: Amgen (Inst), Ipsen (Inst), Lilly (Inst), Bayer (Inst), Roche/Genentech (Inst), AbbVie, Incyte (Inst), Immuneering, Seattle Genetics (Inst), Pfizer (Inst), Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine, Arcus Biosciences (Inst), Stemline Therapeutics, Kanaph Therapeutics, Deciphera, Illumina, Foundation Medicine
Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent WO/2019/055687
Other Relationship: Exelixis, Merck (Inst), AstraZeneca, Lilly, Pancreatic Cancer Action Network, FibroGen, Suzhou Kintor Pharmaceuticals, 1Globe Health Institute, Imugene, Xilis, Replimune, Sun Biopharma, UpToDate
Open Payments Link: https://openpaymentsdata.cms.gov/physician/636276
Andrew H. Ko
Honoraria: Research to Practice, Clinical Care Options, Medscape, BioAscent, MJH Life Sciences, Gerson Lehrman Group
Consulting or Advisory Role: ERYTECH Pharma, Imugene, SynCoreBio, Roche/Genentech, Ipsen, Five Prime Therapeutics, Tyme, Turning Point Therapeutics, Signatera, Syros Pharmaceuticals
Speakers' Bureau: Clinical Care Options
Research Funding: Celgene (Inst), Merck (Inst), Genentech/Roche (Inst), Bristol Myers Squibb (Inst), AbGenomics International (Inst), Apexigen (Inst), Astellas Pharma (Inst), Leap Therapeutics (Inst), BioMed Valley Discoveries (Inst), CrystalGenomics (Inst)
Armando Santoro
Consulting or Advisory Role: Bristol Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ARQULE, Incyte
Speakers' Bureau: Takeda, Roche, AbbVie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, BMS, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD
Joon Oh Park
Consulting or Advisory Role: Celgene, Merck Serono, Servier, AstraZeneca, MediRama
Research Funding: Celgene, MedPacto, Servier, ABL Bio, Eutilex
Marcus S. Noel
Consulting or Advisory Role: Celgene, Taiho Pharmaceutical, Ipsen
Speakers' Bureau: Taiho Pharmaceutical, Celgene, Daiichi Sankyo/Astra Zeneca
Andrew Dean
Stock and Other Ownership Interests: A2A Pharmaceuticals
Honoraria: Amgen
Travel, Accommodations, Expenses: Novartis, Juniper Biologics
Uncompensated Relationships: A2A Pharmaceuticals
Hanno Riess
Leadership: Bayer, BMS GmbH & Co KG, Mylan, Boehringer Ingelheim
Speakers' Bureau: Bayer, BMS GmbH & Co KG
Eric Van Cutsem
Consulting or Advisory Role: Bayer, Lilly, Roche, Servier, Bristol Myers Squibb, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Array BioPharma, Daiichi Sankyo, Pierre Fabre, Taiho Pharmaceutical, Incyte, Astellas Pharma, GlaxoSmithKline, Nordic Group, Pfizer, Takeda, ALX Oncology, AbbVie, BeiGene, Boehringer Ingelheim, Mirati Therapeutics, Seattle Genetics, TERUMO, Zymeworks, Ipsen
Research Funding: Amgen (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Lilly (Inst), Novartis (Inst), Roche (Inst), Ipsen (Inst), Merck (Inst), Merck KGaA (Inst), Servier (Inst), Bristol Myers Squibb (Inst)
Jordan Berlin
Consulting or Advisory Role: Bayer Health, QED Therapeutics, Ipsen, Mirati Therapeutics, Insmed, Oxford BioTherapeutics, Merck KGaA, BioSapien
Research Funding: Bayer (Inst), Incyte (Inst), Karyopharm Therapeutics (Inst), EMD Serono (Inst), Boston Biomedical (Inst), PsiOxus Therapeutics (Inst), Pfizer (Inst), Lilly (Inst), Dragonfly Therapeutics (Inst), AbbVie (Inst), I-MAB (Inst), Astellas Pharma (Inst), Atreca (Inst), Day One Biopharmaceuticals (Inst), Bristol Myers Squibb/Celgene (Inst), Sumitomo Dainippon Pharma Oncology (Inst), 23andMe (Inst), Totus Medicines (Inst), Tyra Biosciences (Inst)
Other Relationship: Novocure, Pancreatic Cancer Action Network, Karyopharm Therapeutics, AstraZeneca
Philip Philip
Honoraria: Celgene, Bayer, Ipsen, Merck, AstraZeneca, TriSalus Life Sciences, Blueprint Medicines, SynCoreBio, Incyte, Bristol Myers Squibb/Medarex, Guardant Health, Rafael Pharmaceuticals, Daiichi Sankyo/Astra Zeneca
Consulting or Advisory Role: Celgene, Ipsen, Merck, TriSalus Life Sciences, Daiichi Sankyo, SynCoreBio, Taiho Pharmaceutical
Speakers' Bureau: Celgene, Bayer, Ipsen, Novartis, Incyte, Bristol Myers Squibb/Medarex
Research Funding: Bayer (Inst), Incyte (Inst), Karyopharm Therapeutics (Inst), Merck (Inst), Taiho Pharmaceutical (Inst), Momenta Pharmaceuticals (Inst), Novartis (Inst), Plexxikon (Inst), Immunomedics (Inst), Regeneron (Inst), Genentech (Inst), TYME (Inst), Caris Life Sciences (Inst), ASLAN Pharmaceuticals (Inst), QED Therapeutics (Inst), Halozyme (Inst), Boston Biomedical (Inst), Advanced Accelerator Applications (Inst), Lilly (Inst), Merus (Inst)
Travel, Accommodations, Expenses: Rafael Pharmaceuticals, Celgene, AbbVie
Uncompensated Relationships: Rafael Pharmaceuticals, Caris MPI
David Goldstein
Honoraria: Sun Biopharma, Boehringer Ingelheim, AstraZeneca
Consulting or Advisory Role: Sun Biopharma, Seattle Genetics, AstraZeneca, Boehringer Ingelheim
Research Funding: Amgen (Inst), Pfizer (Inst), Celgene (Inst), Bayer (Inst), Zucero Therapeutics (Inst), Bristol Myers Squibb (Inst)
Josep Tabernero
Stock and Other Ownership Interests: Oniria Therapeutics
Consulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann LaRoche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, NeoPhore, Orion Biotechnology, Hutchison MediPharma, Scandion Oncology, Ona Therapeutics, SOTIO, Inspirna, Scorpion Therapeutics
Other Relationship: Medscape, MJH Life Sciences, PeerView, Physicians' Education Resource, Imedex/HMP
Mingyu Li
Employment: Ascentage Pharma
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene, Ascentage Pharma
Stefano Ferrara
Employment: SOTIO, BeiGene AG, Bristol Myers Squibb/Celgene/Juno (I)
Stock and Other Ownership Interests: BeiGene
George Zhang
Employment: Bristol Myers Squibb/Celgene
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene
Brian Lu
Employment: Bristol Myers Squibb/Celgene
Stock and Other Ownership Interests: Bristol Myers Squibb/Celgene
Andrew V. Biankin
Employment: AstraZeneca/MedImmune, BMSi
Leadership: Cambridge Cancer Genomics, Concr, Wollemia Oncology, Gabriel Precision Oncology, Cumulus Oncology
Stock and Other Ownership Interests: Cumulus Oncology, Modulus Oncology, Wollemia Oncology, Concur, Cambridge Cancer Genomics, Gabriel Precision Oncology, Humans.ai
Honoraria: Havas Lynx Group
Consulting or Advisory Role: AstraZeneca/MedImmune
Speakers' Bureau: Celgene
Research Funding: Celgene (Inst), AstraZeneca/MedImmune (Inst)
Patents, Royalties, Other Intellectual Property: Agilent Technologies—Royalty payments to Institute (University of Glasgow)
Michele Reni
Consulting or Advisory Role: Celgene, Lilly, AstraZeneca, Panavance Therapeutics, Viatris, SOTIO, Servier, MSD/AstraZeneca
Research Funding: Celgene (Inst), AstraZeneca (Inst)
Travel, Accommodations, Expenses: Celgene
Other Relationship: Celgene, AstraZeneca
No other potential conflicts of interest were reported.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data requests may be submitted to Celgene, a Bristol Myers Squibb Company, at https://vivli.org/ourmember/celgene/ and must include a description of the research proposal.