Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial

PURPOSE

In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed BRCA1- and/or BRCA2-mutated advanced ovarian cancer compared with placebo (hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41; median not reached v 13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors.

PATIENTS AND METHODS

Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete [CR] or partial response [PR]), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status (BRCA1 or BRCA2). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate.

RESULTS

The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a BRCA1 or BRCA2 mutation, respectively.

CONCLUSION

Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.

INTRODUCTION

For patients with newly diagnosed advanced ovarian cancer (OC), the standard of care is cytoreductive surgery and platinum-based chemotherapy.^1,2 Most patients have no evidence of disease (NED) after treatment, but approximately 70% will relapse within 3 years of diagnosis.² After recurrence, most patients receive multiple additional lines of treatment and will eventually die as a result of the disease.

CONTEXT

• Key Objective

• To explore whether all patients receiving first-line olaparib maintenance (compared with surveillance alone) will benefit from treatment regardless of baseline characteristics (preselected covariates), including those with favorable prognostic features (eg, patients with complete cytoreduction, those with complete response after platinum-based chemotherapy, or those with stage III disease who underwent upfront surgery and had no gross residual disease), or BRCA mutation status and report objective response rate to better understand the olaparib treatment effect in patients with newly diagnosed BRCA-mutated advanced ovarian cancer.

• Knowledge Generated

• SOLO1 subgroup analyses of PFS reported here were consistent with those previously reported in the overall study population, demonstrating that olaparib maintenance therapy was of substantial benefit in all reported patient subgroups.

• Relevance

• Regardless of patient baseline outcomes from surgery and chemotherapy or BRCA mutation type, patients with newly diagnosed advanced ovarian cancer are at high risk of disease progression and benefit from maintenance olaparib treatment.

Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has demonstrated efficacy in several tumor types, including advanced OC, breast, prostate, and pancreatic cancers.^3-7 Olaparib is approved in the United States, the European Union, and other countries as maintenance treatment for women with germline or somatic BRCA-mutated advanced OC who are in response to first-line platinum-based chemotherapy based on the phase III SOLO1 study (ClinicalTrials.gov identifier: NCT01844986).^8,9 SOLO1¹⁰ reported a substantial improvement in progression-free survival (PFS) after maintenance olaparib (tablets) versus placebo in patients with newly diagnosed advanced OC and a BRCA1 or BRCA2 mutation (Kaplan-Meier estimate of rate of freedom from disease progression or death at 3 years, 60% v 27%, respectively; hazard ratio [HR], 0.30; 95% CI, 0.23 to 0.41). In contrast to some contemporary trials in this setting (GOG-0218,¹¹ ENGOT-OV26/GOG-3012/PRIMA,¹² IMagyn050,¹³ AGO-OVAR16¹⁴), SOLO1 recruited patients regardless of prior surgical status; patients could have undergone upfront or interval cytoreductive surgery and have residual or no gross residual disease; however, in SOLO1, patients were required to have a BRCA-mutated tumor.

Baseline factors that may affect outcomes of patients with newly diagnosed advanced OC include tumor response (complete response [CR] v partial response [PR]) after platinum-based chemotherapy, BRCA mutation status, and timing of cytoreductive surgery (interval v upfront), as well as outcomes after surgery (residual v no gross residual disease).^15,16 Surgical outcome has been reported as 1 of the most important independent prognostic factors for survival,¹⁶ with a significant survival advantage observed in patients with no gross residual disease compared with those with residual tumor burden of 1 to 10 mm or > 10 mm in diameter.¹⁷ We wished to explore whether all patients receiving first-line olaparib maintenance (compared with surveillance alone) benefit from treatment regardless of baseline characteristics, including those with favorable prognostic features (eg, complete cytoreduction or CR after platinum-based chemotherapy). In patients with no evidence of gross residual disease after surgery, it is likely that micrometastatic disease remains in almost all cases, and the risk of recurrence remains high¹⁸; despite being associated with a better prognosis, most of these patients will experience relapse later. It is possible that these patients may obtain even greater benefit from maintenance olaparib than those who have evidence of disease at baseline, because patients who initiate treatment with NED have longer PFS versus those with evidence of disease at baseline.^19-21

We report the efficacy of olaparib in SOLO1 in terms of PFS using preselected baseline characteristics of surgical status and response after completion of platinum-based chemotherapy, patients with stage III disease who underwent upfront surgery and had no gross residual disease, and BRCA mutation status. We also report objective response rate (ORR) evaluated in women with radiologic evidence of disease at baseline to better understand the olaparib treatment effect in patients with newly diagnosed BRCA-mutated advanced OC.

PATIENTS AND METHODS

Study Design

SOLO1 was a phase III, multicenter, randomized, double-blind study.¹⁰ Patients had newly diagnosed confirmed advanced (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV) high-grade serous or endometrioid OC, primary peritoneal cancer, and/or fallopian tube cancer, were in clinical CR (defined as no radiologic evidence of disease and normal cancer antigen–125 [CA-125] level) or PR (≥ 30% decrease in sum of diameters of target lesions or no radiologic evidence of disease after chemotherapy but abnormal CA-125 level) after platinum-based chemotherapy, and had deleterious or suspected deleterious germline or somatic BRCA mutation (Data Supplement provides testing details). Patients with stage III disease had undergone cytoreductive surgery before chemotherapy (upfront) or after initiation but before completion of chemotherapy (interval), and those with stage IV disease had undergone biopsy and/or upfront or interval cytoreductive surgery. Full inclusion/exclusion criteria have been published previously.¹⁰

Study Treatments

After completion of first-line platinum-based chemotherapy, patients were randomly assigned 2:1 to maintenance olaparib tablets (300 mg twice daily) or placebo (Fig 1). Random assignment was stratified according to clinical response after platinum-based chemotherapy (CR or PR). Treatment was continued until investigator-assessed objective disease progression (modified Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1). After 2 years of treatment, patients with CR or NED discontinued treatment; those with evidence of disease could continue treatment.¹⁰

FIG 1.

CONSORT diagram.

Study Outcome Measures

The primary efficacy analysis data cutoff (DCO) was May 17, 2018.¹⁰ Subgroup analyses reported here evaluated investigator-assessed PFS by modified RECIST (version 1.1) at the primary DCO. We used preselected covariates defined as clinically relevant for study patients. Prespecified subgroup analyses included clinical response after platinum-based chemotherapy (CR or PR) and BRCA mutation status (BRCA1/BRCA2). Subgroup efficacy analyses were also performed based on timing of surgery (upfront/interval; exploratory) and surgery outcome (macroscopic residual or no gross residual disease; prespecified) reported using data collected by electronic case report form (eCRF). PFS was also evaluated in patients with stage III disease with no gross residual disease after upfront surgery to determine the value of maintenance olaparib in patients with favorable prognostic features.

ORR (modified RECIST) was a secondary end point evaluated in women with radiologic evidence of disease at baseline. ORR was calculated based on overall visit responses from each postbaseline RECIST assessment (investigator assessed) before detection of progression or initiation of subsequent anticancer therapy.

Statistical Analysis

For subgroup analyses of PFS, the HRs (olaparib:placebo) and associated 95% CIs were calculated from a Cox proportional hazards model that contained the treatment term, factor (subgroup), and treatment-by-factor interaction term. CIs were calculated using a profile likelihood approach.²² An HR < 1 favored olaparib. Subgroup analyses of PFS were not powered to detect a statistically significant difference between subgroups evaluated. ORR was summarized by the number and percentage of patients with measurable disease at baseline. Statistical analyses were performed with SAS (version 9.4; SAS Institute, Cary, NC).

RESULTS

Patient Characteristics

Patient characteristics were generally well balanced between treatment groups (Table 1).¹⁰ Overall, 282 patients (72%) had a BRCA1 mutation, 106 (27%) had a BRCA2 mutation, and 3 (1%) had both. Patient baseline characteristics for BRCA mutation (Table 1) and other subgroups (Data Supplement) were generally balanced.

TABLE 1.

Baseline Patient Characteristics for the Overall Study Population and According to Patient BRCA Mutation Status

PFS According to Subgroup Analysis

At DCO, median follow-up was approximately 41 months in both arms. In the olaparib arm, median treatment duration was 24.6 months, consistent with the 2-year prespecified treatment duration; for placebo, this was 13.9 months, consistent with the median PFS reported.

Surgical status.

In total, 63% and 35% of patients underwent upfront and interval surgery, respectively; 21% and 76% had residual and no gross residual disease, respectively.

The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (median PFS, not reached [NR] v 15.3 months, respectively; HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (33.6 v 9.8 months; HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront and interval surgery, respectively (Fig 2A), and by 56% (29.4 v 11.3 months; HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (NR v 15.3 months; HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual and no gross residual disease after surgery, respectively (Fig 2B). Similar results were observed for patients with or without residual disease after upfront surgery (Table 2).

FIG 2.

Kaplan-Meier estimates of investigator-assessed progression-free survival (PFS) for subgroup analyses based on (A) surgery timing, (B) residual macroscopic disease status, (C) patients with stage III disease who underwent upfront surgery and had no gross residual disease, (D) response after platinum-based chemotherapy at baseline, and (E) BRCA mutation status. CR, complete response; HR, hazard ratio; NR, not reached; PR, partial response.

TABLE 2.

Investigator-Assessed PFS After Upfront Surgery Based on Residual Disease Status

Kaplan-Meier estimates of the percentage of patients who had undergone upfront surgery, received olaparib, and were progression free at 1, 2, and 3 years were 91%, 78%, and 69% (v 58%, 40%, and 32% receiving placebo), respectively; for those who underwent interval surgery, estimates were 83%, 66%, and 47% (v 43%, 26%, and 19%), respectively (Fig 3A). For patients who had residual macroscopic disease after cytoreductive surgery before entry into the study, 79%, 60%, and 48% of patients who received olaparib were progression free at 1, 2, and 3 years (v 41%, 28%, and 24% who received placebo), respectively; for patients who had no gross residual disease at study entry, the percentages for olaparib-treated patients were 90%, 77%, and 65% (v 57%, 38%, and 29% who received placebo; Fig 3B), respectively.

FIG 3.

Proportion of patients free of progression or death over time for subgroup analysis–based Kaplan-Meier estimates for (A) surgery timing (8 patients had no surgery or were missing timing data [olaparib arm, n = 5; placebo arm, n = 3]), (B) residual macroscopic disease status, (C) response after platinum-based chemotherapy at baseline, and (D) BRCA mutation status (3 patients [all in olaparib arm] had both BRCA1 and BRCA2 mutations and were progression free up to 42 months). CR, complete response; PR, partial response. (^a) Based on Kaplan-Meier estimates.

Forty-four percent of patients with stage III disease (mostly stage IIIC) underwent upfront surgery and had no gross residual macroscopic disease after surgery. For these patients, the risk of disease progression or death was reduced by 68% in patients receiving olaparib compared with placebo (median PFS, NR v 21.9 months; HR, 0.32; 95% CI, 0.20 to 0.51; Fig 2C). Of those receiving olaparib, 92%, 81%, and 71% were progression free at 1, 2, and 3 years (v 66%, 45%, and 35% who received placebo), respectively. Additional data for patients with stage III disease are provided in the Data Supplement.

Response after platinum-based chemotherapy.

On the basis of eCRF data, 74% of women entered the study with no target or nontarget lesions and normal CA-125 (clinical CR), and 26% had a ≥ 30% reduction in the sum of diameters of target lesions, taking as reference the baseline sum diameters from start to end of chemotherapy, or NED in the posttreatment scan but with a CA-125 level that had not decreased to within the normal range (PR; 35% of patients in PR had status determined by elevated CA-125 level). Risk of disease progression or death was reduced for patients receiving olaparib compared with placebo by 66% in women in clinical CR (median PFS, NR v 15.3 months; HR, 0.34; 95% CI, 0.24 to 0.47) and by 69% in women with a PR at baseline (30.9 v 8.4 months; HR, 0.31; 95% CI, 0.18 to 0.52; Fig 2D). On the basis of Kaplan-Meier estimates, the percentages of patients with a baseline CR who received olaparib and were progression free at 1, 2, and 3 years were 91%, 77%, and 65% (v 58%, 39%, and 29% receiving placebo), respectively, and those of patients with a baseline PR were 79%, 64%, and 50% (v 30%, 20%, and 20% Fig 3C), respectively.

BRCA mutation status.

At the primary DCO, 155 patients in the BRCA1-mutated group (55%), 43 in the BRCA2-mutated group (41%), and none in the BRCA1- and BRCA2-mutated group (n = 3) experienced disease progression. Patients receiving placebo who had a BRCA1 mutation or BRCA2 mutation had a median PFS of 13.8 months; this was substantially increased for patients who received olaparib, with a greater PFS benefit observed for those with a BRCA2 mutation (median PFS, NR) relative to a BRCA1 mutation (41.4 months; Fig 2E). Kaplan-Meier estimates of the percentage of BRCA1-mutated patients who received olaparib and were progression free at 1, 2, and 3 years were 86%, 69%, and 53% (v 52%, 36%, and 26% receiving placebo), respectively, and those of BRCA2-mutated patients were 92%, 85%, and 80% (v 50%, 32%, and 29%; Fig 3D), respectively. The risk of disease progression or death was reduced for olaparib-treated patients versus those receiving placebo by 59% (HR, 0.41; 95% CI, 0.30 to 0.56) for BRCA1-mutated patients and by 80% (HR, 0.20; 95% CI, 0.10 to 0.37) for BRCA2-mutated patients (Fig 2E).

ORR

Among women with radiologic evidence of disease at baseline (target and nontarget lesions; RECIST), ORR was 43% (n = 23) in the olaparib arm and 23% (n = 6) in the placebo arm (Table 3). CRs were reported for 28% (n = 15) of olaparib-treated patients compared with 12% (n = 3) of patients receiving placebo, and PRs were reported for 15% (n = 8) and 12% (n = 3) olaparib- and placebo-treated of patients, respectively. In patients with an objective response, median time from random assignment to onset of response and median duration of response were 10.8 and 28.2 months for olaparib and 5.4 and 8.6 months for placebo, respectively.

TABLE 3.

Best Objective Response in Women With Radiologic Evidence of Disease at Baseline

DISCUSSION

The SOLO1 subgroup analyses of PFS reported here were consistent with those in the overall study population,¹⁰ demonstrating that olaparib maintenance therapy was substantially beneficial in all reported preselected patient subgroups.

Olaparib demonstrated considerable benefit in the 44% of women in SOLO1 with stage III disease who had undergone upfront surgery and had no gross residual disease, a population ineligible for several recent first-line trials. Despite optimal surgical results, these patients are still at substantial risk of disease recurrence and should be offered olaparib maintenance treatment. In addition, although they had no evidence of gross residual disease, micrometastatic disease probably remains in almost all cases.¹⁸ SOLO1 was designed to reflect clinical practice by including all patients with advanced OC regardless of surgical outcome. Our data demonstrate that all BRCA-mutated patients with advanced OC should be considered at high risk of progression and receive appropriate treatment, such as olaparib maintenance, to provide the best chance of delaying disease progression. Additionally, we found that maintenance olaparib improved outcomes compared with placebo, regardless of whether patients had radiologic evidence of disease at baseline. In these patients, maintenance olaparib induced CR in 28% of women, more than double that observed with placebo (12%).

The overall proportion of patients with no gross residual disease after surgery in SOLO1 was slightly higher (77% and 75% of patients in the olaparib and placebo groups, respectively) than may be expected (rate of complete resection in unselected patients with advanced-stage OC ranged between 50% and 70% in surgically specialized gynecologic cancer centers)²³; our study results may reflect expertise of surgeons at clinical study sites or different characteristics of BRCA mutation versus sporadic high-grade serous cancers²⁴ rather than patient selection bias. As noted, the SOLO1 population reflects clinical practice and represents 1 of the largest phase III studies in advanced BRCA-mutated OC surgical patients. Furthermore, baseline characteristics were balanced between arms within subgroups analyzed; therefore, outcomes related to timing of surgery or residual disease status after surgery are unlikely to be influenced by baseline differences.

Efficacy results observed in the placebo arm of this study demonstrate that all patients with advanced high-grade OC should be considered at high risk of progression. Despite a large proportion of patients having optimal surgical outcomes and being in CR after chemotherapy, outcomes after placebo treatment were poor, further supporting the use of maintenance olaparib for all patients regardless of baseline characteristics. Although the differential effect of PARP inhibitors in maintenance and treatment settings has not been formally evaluated, olaparib reduced risk of disease progression and death for patients with CR or PR at baseline. There may be different prognostic factors for patients who enter the study in CR compared with PR, and we cannot compare the magnitude of benefit between the 2 subgroups based on an exploratory analysis. However, we can conclude that both subgroups of patients derived meaningful benefit from olaparib treatment, with 30% (olaparib, 50% v placebo, 20%) and 36% (olaparib, 65% v placebo, 29%) more patients being progression free at 3 years in the PR and CR groups, respectively. Similar results were observed in the relapsed setting.²¹ For patients who initiate olaparib in CR, the goal of treatment is to delay their disease relapse, and for patients with PR, it is to potentially induce CR and/or delay relapse and the need for subsequent chemotherapy.

Among women with evidence of disease at baseline, nearly twice as many had an objective response while receiving olaparib maintenance (43%) compared with placebo (23%). Reasons for patients receiving placebo (ie, not active treatment) experiencing a response may include a carryover effect from platinum-based chemotherapy, timing of patient scans (baseline followed by scans once every 3 months), or variability in measuring RECIST.²⁵ Of note, the ORR analysis reported classified patients as being in clinical CR or PR based on eCRF data, whereas the primary analysis used the randomization code.¹⁰

Consistent with previous prevalence studies, in SOLO1, BRCA1 mutation was more frequent in patients with newly diagnosed advanced OC than BRCA2 mutation.²⁶ A significant PFS benefit with olaparib versus placebo was demonstrated for all patients, regardless of mutation type; medium PFS in the placebo arm was consistent for both BRCA1- and BRCA2-mutated patients. Statistical tests were not used to compare BRCA1- and BRCA2-mutated patients; however, those with a BRCA2 mutation (PFS HR, 0.20) seemed to receive greater benefit from maintenance olaparib than those with a BRCA1 mutation (HR, 0.41), although the small size of the BRCA2-mutated subgroup and potential imbalances in baseline characteristics (ie, more adverse prognostic factors in the placebo v olaparib arm) should be noted (baseline characteristics were generally balanced for BRCA1- and BRCA2-mutated patients combined). By 2 years, only 12 BRCA2-mutated patients remained at risk for progression in the placebo arm. It therefore seems a BRCA2 mutation may be a marker of response to olaparib rather than a prognostic indicator in SOLO1. This trend for differential benefit between BRCA1- and BRCA2-mutated patients was not reported with olaparib maintenance therapy for platinum-sensitive relapsed OC in SOLO2⁶ (data on file, AstraZeneca, Cambridge, UK; ClinicalTrials.gov identifier: NCT01874353), although enrichment of BRCA2 mutation was observed among long-term responders to olaparib in Study 19.²⁷ One explanation for this could be resistance mechanisms associated with BRCA1. One mechanism is the production of functional hypomorphic isoforms of BRCA1 protein from alternative messenger RNA splicing, which has been reported to contribute to resistance to platinum-based chemotherapy and PARP inhibition.²⁸ In a subanalysis of GOG-0218, PFS was increased in patients with a BRCA2 versus BRCA1 mutation (median, 21.6 v 15.7 months) regardless of treatment received.²⁹ However, in SOLO1, median PFS and Kaplan-Meier estimates at 1, 2, and 3 years were similar for BRCA1- and BRCA2-mutated patients who received placebo.

A limitation of our analyses is the relatively small patient numbers in some subgroups, including those receiving interval debulking surgery (n = 94 and 43 for olaparib and placebo, respectively), those with residual disease after surgery (n = 55 and 29, respectively), and those in clinical PR after platinum-based chemotherapy (n = 71 and 30, respectively). Although relatively small subgroups, patients receiving olaparib maintenance treatment benefited from treatment.

In conclusion, maintenance therapy with olaparib provided a substantial PFS benefit among women with newly diagnosed advanced OC and a BRCA mutation. This PFS benefit with olaparib was achieved in all subgroups irrespective of surgery timing, residual disease status after surgery, response after platinum-based chemotherapy (CR or PR), or type of BRCA mutation. Continued follow-up of these patients is important to provide information on which subsets of patients will remain progression free and have NED long-term. These data demonstrate that regardless of patient baseline outcomes from surgery and chemotherapy or BRCA mutation type, patients with newly diagnosed advanced OC are at high risk of disease progression and benefit from maintenance olaparib treatment.

AUTHOR CONTRIBUTIONS

Conception and design: Charlie Gourley, Amit Oza, Elizabeth S. Lowe, Kathleen N. Moore

Provision of study material or patients: Paul DiSilvestro, Nicoletta Colombo, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Amit Oza, Carol A. Aghajanian, Cara A. Mathews, Joyce Liu, Kathleen N. Moore

Collection and assembly of data: Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, Michael Friedlander, Alla Lisyanskaya, Charlie Gourley, Amit Oza, William H. Bradley, Cara A. Mathews, Joyce Liu, Elizabeth S. Lowe, Kathleen N. Moore

Data analysis and interpretation: Paul DiSilvestro, Nicoletta Colombo, Byoung-Gie Kim, Ana Oaknin, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Susana Banerjee, Amit Oza, Antonio González-Martín, Carol A. Aghajanian, William H. Bradley, Cara A. Mathews, Elizabeth S. Lowe, Ralph Bloomfield, Kathleen N. Moore

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

Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 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.

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Paul DiSilvestro

Consulting or Advisory Role: AstraZeneca

Research Funding: Janssen Oncology (Inst), Tesaro (Inst), AstraZeneca (Inst), Genentech (Inst), AbbVie (Inst)

Nicoletta Colombo

Honoraria: Roche/Genentech, AstraZeneca, Tesaro, PharmaMar

Consulting or Advisory Role: Roche/Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Takeda, Tesaro, BioCad, GlaxoSmithKline

Giovanni Scambia

Consulting or Advisory Role: Clovis Oncology, AstraZeneca, PharmaMar, Roche, Tesaro

Speakers’ Bureau: Clovis Oncology Italy, Merck Sharp & Dohme Italy

Ana Oaknin

Consulting or Advisory Role: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Immunogen, Genmab

Research Funding: AbbVie Deutschland (Inst), Ability Pharma (Inst), Advaxis (Inst), Aeterna Zentaris (Inst), Amgen (Inst), Aprea Therapeutics (Inst), Clovis Oncology (Inst), Eisai (Inst), F. Hoffmann-La Roche (Inst), Regeneron Pharmaceuticals (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche

Michael Friedlander

Honoraria: AstraZeneca, Merck Sharp & Dohme, Lilly, Takeda, Novartis

Consulting or Advisory Role: AstraZeneca, Merck Sharp & Dohme, AbbVie, Lilly, Takeda, Novartis

Speakers’ Bureau: AstraZeneca, ACT Genomics

Research Funding: BeiGene (Inst), AstraZeneca (Inst)

Travel, Accommodations, Expenses: AstraZeneca

Alla Lisyanskaya

Honoraria: Incuron (Inst), Merck Sharp & Dohme (Inst), AstraZeneca (Inst), Regeneron (Inst), Roche (Inst)

Research Funding: Incuron, Roche, AstraZeneca, Regeneron, Merck Sharp & Dohme

Anne Floquet

Consulting or Advisory Role: Roche, MSD Oncology, GlaxoSmithKline, Tesaro, Clovis Oncology, AstraZeneca

Travel, Accommodations, Expenses: Roche, AstraZeneca, Clovis Oncology, GlaxoSmithKline, Tesaro, MSD Oncology

Alexandra Leary

Honoraria: AstraZeneca, Clovis Oncology

Consulting or Advisory Role: Clovis Oncology (Inst), AstraZeneca (Inst), Tesaro (Inst), BioCad, Gritstone Oncology, Seattle Genetics, Ability Pharma (Inst), Merck Sharp & Dohme (Inst), GlaxoSmithKline (Inst), Merck Serono (Inst)

Research Funding: Merus (Inst), GamaMabs Pharma (Inst), Inivata (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Tesaro

Gabe S. Sonke

Consulting or Advisory Role: Novartis (Inst)

Research Funding: Roche (Inst), AstraZeneca (Inst), Novartis (Inst), Merck Sharp & Dohme (Inst)

Charlie Gourley

Research Funding: AstraZeneca

Honoraria: Tesaro, Cor2Ed, GlaxoSmithKline, MSD Oncology, Clovis Oncology

Consulting or Advisory Role: AstraZeneca, Nucana (Inst), Tesaro (Inst), Cor2Ed, Sierra Oncology, GlaxoSmithKline, MSD Oncology

Research Funding: AstraZeneca (Inst), Novartis (Inst), Aprea (Inst), Nucana (Inst), Tesaro (Inst), GlaxoSmithKline (Inst), MSD Oncology (Inst)

Patents, Royalties, Other Intellectual Property: One patent issued and 4 pending for a gene expression signature to predict cancer sensitivity to antiangiogenic therapy (Inst)

Susana Banerjee

Honoraria: Roche

Consulting or Advisory Role: AstraZeneca/MedImmune, Tesaro, Clovis Oncology, Merck, Seattle Genetics, Genmab, Carrick Therapeutics (Inst), Amgen, Roche, GlaxoSmithKline, MSD Oncology

Research Funding: AstraZeneca (Inst), Janssen-Cilag (Inst), GlaxoSmithKline (Inst), NuCana BioMed

Travel, Accommodations, Expenses: AstraZeneca

Amit Oza

Uncompensated Relationships: Ozmosis Research

Antonio González-Martín

Consulting or Advisory Role: Roche, Tesaro/GlaxoSmithKline, Clovis Oncology, AstraZeneca, Merck Sharp & Dohme, Genmab, Immunogen, Oncoinvent, Pfizer/EMD Serono, Amgen

Speakers’ Bureau: Roche, AstraZeneca, Tesaro/GlaxoSmithKline, PharmaMar, Roche (Inst), Tesaro/GlaxoSmithKline (Inst)

Travel, Accommodations, Expenses: Roche, AstraZeneca, PharmaMar, Tesaro/GlaxoSmithKline

Carol A. Aghajanian

Consulting or Advisory Role: Tesaro, Mersana, Eisai, Roche

Research Funding: Genentech/Roche (Inst), AbbVie (Inst), Clovis Oncology (Inst), AstraZeneca (Inst)

William H. Bradley

Consulting or Advisory Role: Celsion, Inovio Pharmaceuticals

Travel, Accommodations, Expenses: Inovio, Clovis Oncology

Cara A. Mathews

Research Funding: AstraZeneca (Inst), Tesaro/GlaxoSmithKline (Inst), Syros (Inst), Astellas Pharma (Inst), Seattle Genetics (Inst), Deciphera (Inst)

Joyce Liu

Consulting or Advisory Role: Tesaro, Mersana, Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Regeneron

Research Funding: Genentech/Roche (Inst), AstraZeneca (Inst), Boston Biomedical (Inst), Atara Biotherapeutics (Inst), Acetylon (Inst), Bristol Myers Squibb (Inst), Agenus (Inst), CytomX Therapeutics (Inst), Regeneron (Inst), Tesaro (Inst), Clovis Oncology (Inst), Surface Oncology (Inst), 2X Oncology (Inst), Vigeo Therapeutics (Inst), Aravive (Inst), Arch Oncology (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Merck

Uncompensated Relationships: Merck, AstraZeneca

Elizabeth S. Lowe

Employment: AstraZeneca

Stock and Other Ownership Interests: AstraZeneca

Ralph Bloomfield

Employment: AstraZeneca

Stock and Other Ownership Interests: AstraZeneca

Kathleen N. Moore

Honoraria: Research To Practice, Prime Oncology

Consulting or Advisory Role: Genentech/Roche, Immunogen, AstraZeneca (Inst), Clovis Oncology, Tesaro (Inst), VBL Therapeutics, Janssen Oncology, Merck, Aravive, Samumed, OncoMed, Pfizer/EMD Serono, Eisai, AbbVie, Vavotar, Mersana (Inst)

Research Funding: PTC Therapeutics (Inst), Lilly (Inst), Merck (Inst), Tesaro (Inst), Genentech (Inst), Clovis Oncology (Inst), Lilly Foundation (Inst), Regeneron (Inst), Advaxis (Inst), Bristol Myers Squibb (Inst), Verastem (Inst), Novartis Pharmaceuticals UK (Inst), AstraZeneca (Inst), Agenus (Inst), Takeda (Inst), Forty Seven (Inst), Stem CentRx (Inst), Immunogen (Inst), Bayer (Inst), Novogen (Inst), AbbVie/Stemcentrx (Inst)