Abstract
Background
INAVO120 (NCT04191499) demonstrated significantly improved progression-free/overall survival with inavolisib plus palbociclib–fulvestrant versus placebo plus palbociclib–fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-resistant advanced breast cancer. We provide comprehensive analyses of key selected adverse events and their management.
Materials and methods
Inavolisib was given 9 mg orally once daily on days 1-28 of each 28-day cycle; palbociclib, at 125 mg orally once daily on days 1-21; fulvestrant, at 500 mg intramuscularly on days 1 and 15 of cycle 1, and every ∼28 days thereafter. Supportive therapies were used as clinically indicated. Key selected adverse events assessed included hyperglycaemia, stomatitis/mucosal inflammation, rash and diarrhoea, graded per National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.
Results
Data cut-off was 29 September 2023; median follow-up was 21.3 months (range 0-43.1; inavolisib arm) and 21.5 months (0.1-40.3; placebo arm). Inavolisib dose interruptions, reductions and discontinuations due to hyperglycaemia were observed in 27.2%, 2.5% and 0.6% of patients, respectively; the median time to first onset was 7.0 days (range 2.0-955.0). Metformin was the most commonly used antihyperglycaemic. No patients in the prediabetic population discontinued inavolisib due to hyperglycaemia. Inavolisib dose interruptions, reductions and discontinuations due to rash were observed in 1.2%, 0.6% and 0% of patients, respectively; the median time to first onset was 29.0 days (range 1.0-952.0). Topical hydrocortisone was most commonly used. Inavolisib dose interruptions, reductions and discontinuations due to stomatitis/mucosal inflammation were observed in 9.9%, 3.7% and 0.6% of patients, respectively; the median time to first onset was 13.0 days (range 1.0-610.0). Dexamethasone mouthwash was most commonly used. Inavolisib dose interruptions, reductions and discontinuations due to diarrhoea were observed in 6.8%, 1.2% and 0% of patients respectively; the median time to first onset was 13.0 days (range 1.0-610.0). Loperamide was most commonly used. Data were largely comparable across regions and ages. Inavolisib’s safety profile was consistent with that of long-term treated populations.
Conclusions
This analysis demonstrates the generally consistent, manageable and tolerable safety profile of inavolisib plus palbociclib–fulvestrant. Key selected adverse events were generally reversible and were controlled by concomitant medications and dose modifications.
Key words: diarrhoea, hyperglycaemia, inavolisib, PIK3CA, rash, stomatitis/mucosal inflammation
Highlights
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INAVO120 demonstrates the generally consistent, manageable and tolerable safety profile of the inavolisib-based regimen.
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Key selected adverse events were generally nonserious, low-grade, and mostly occurred in early treatment cycles.
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These events were generally reversible and were controlled by concomitant medications and dose modifications.
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Subgroup analyses showed numerical differences in certain adverse events, but they were manageable overall.
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The long-term safety profile was consistent with previous reports.
Introduction
Inavolisib is an oral, highly potent and α-selective phosphoinositide 3-kinase (PI3K) inhibitor that also promotes mutated p110α degradation.1 The phase III, randomised, double-blind, placebo-controlled INAVO120 study (NCT04191499) assessed first-line inavolisib/placebo with palbociclib–fulvestrant in PIK3CA-mutated, hormone receptor-positive, HER2-negative, endocrine-resistant advanced breast cancer.2 INAVO120 met its primary endpoint (clinical cut-off, 29 September 2023): inavolisib plus palbociclib–fulvestrant resulted in a significant progression-free survival (PFS) benefit versus placebo plus palbociclib–fulvestrant [hazard ratio 0.43, 95% confidence interval (CI) 0.32-0.59, P<0.001; medians, 15.0 (95% CI 11.3-20.5) and 7.3 months (95% CI, 5.6-9.3), respectively].2 The updated PFS hazard ratio at the final analysis (clinical cut-off, 15 November 2024) was 0.42 [95% CI 0.32-0.55; medians, 17.2 (95% CI 11.6-22.2) and 7.3 months (95% CI 5.9-9.2), respectively] and overall survival (OS) was also significantly improved [hazard ratio 0.67 (95% CI 0.48-0.94; P=0.02; final OS boundary 0.0469); medians, 34.0 (95% CI 28.4-44.8) and 27.0 months (95% CI 22.8-38.7), respectively].3
INAVO120 confirmed that inavolisib can be combined with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine therapy at full doses of each agent, with an acceptable, manageable safety and tolerability profile.2, 3, 4 In-depth knowledge of the safety profile of novel therapeutics is crucial for associated adverse event management. We provide comprehensive analyses of key selected adverse events and their management and an overview of inavolisib’s safety profile in selected subgroups.
Materials and methods
Study design and procedures
The study design and protocol have been published.2 INAVO120 enrolled pre-, peri- and postmenopausal women, and men, with measurable disease by RECIST v1.1,5 endocrine-resistant disease by European Society for Medical Oncology criteria,6 fasting glucose <126 mg/dL (<7.0 mmol/L) and glycated haemoglobin (HbA1c) <6.0% (amended from <5.7% to more closely align with the eligible threshold for fasting glucose including prediabetes per the American Diabetes Association). Patients with type 1 or 2 diabetes requiring ongoing treatment were excluded.
Patients were randomly assigned 1:1 to inavolisib [9 mg orally (p.o.) once daily (qd) on days 1-28 of each 28-day cycle]/placebo (p.o. qd) with palbociclib (125 mg p.o. qd on days 1-21 of each 28-day cycle) plus fulvestrant (500 mg intramuscularly on cycle 1, days 1 and 15, and every ∼28 days thereafter). Stratification factors were visceral disease (yes versus no), endocrine resistance (primary versus secondary6) and region [North America or Western Europe versus Asia versus Other (see Appendix for countries comprising each category)].
Inavolisib dose modifications, including interruptions, were permitted; reductions were to 6 mg qd and then 3 mg qd. Palbociclib dose modifications were permitted per local prescribing information. Fulvestrant dose reductions were not permitted (interruptions were). Treatment continued until disease progression, unacceptable toxicity, consent withdrawal or death.
Supportive therapies were used as clinically indicated, per local standard practise. Antiemetic and antidiarrhoeal medications were not administered prophylactically before initial study treatment; they could be used per standard clinical practice before subsequent study drug doses. To reduce stomatitis risk, dexamethasone alcohol-free mouthwashes were allowed to be used per the SWISH study.7 Prophylactic metformin for hyperglycaemia was allowed (primary prophylaxis was recommended at the investigator’s discretion, where allowed by local regulations, and could be initiated on cycle 1, day 1 for patients at high risk); no prophylaxis for rash was recommended. Further details are available in the published protocol.2
INAVO120 was performed in accordance with the the International Council for Harmonisation (ICH) E6 guideline for Good Clinical Practice and the principles of the Declaration of Helsinki.
Safety assessments
Safety monitoring included assessment of the nature, frequency and severity of adverse events, with severity graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.2 All events were reported after study drug initiation until 30 days after the final dose of study treatment or initiation of another anticancer therapy, whichever occurred first.
Key selected adverse events included hyperglycaemia, stomatitis/mucosal inflammation, rash and diarrhoea; grouped terms for these and other selected events are defined in the Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735.
Adverse event management
Standard-of-care measures and adverse event management guidelines utilising dose modifications and interruptions were effective in managing adverse events, as reflected by the high relative dose intensity maintained and by low treatment discontinuation due to adverse events.2 For hyperglycaemia, time was allowed (up to 7 days) for resolution after interruptions and antihyperglycaemic treatment to avoid premature dose reduction or discontinuation. Insulin or sulphonylureas were recommended to be administered with caution, as subsequent inavolisib interruption could lead to rapid insulin level escalation and hypoglycaemia.8 Summaries of key selected adverse event management and follow-up are reported in the Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735, including additional guidelines for patients at high risk of hyperglycaemia that were added to the protocol.
Statistical analysis
The Safety Analysis Set (SAS) comprised all patients who received ≥1 dose of any study drug.2 The Full Analysis Set (FAS) included all randomly assigned patients.2 Patients in the SAS were analysed by treatment received.
Median and range or interquartile range were used for continuous variables and patient counts and percentages for categorical variables. Crude methods were used for analyses of time to onset of key selected adverse events (only including patients who had such events).
Results
Patient characteristics
INAVO120 enrolled 325 patients in 28 countries between 29 January 2020 and 14 September 2023; the clinical cut-off for this analysis was 29 September 2023.2 Median follow-up was 21.3 months (range 0-43.1) in the inavolisib arm and 21.5 months (0.1-40.3) in the placebo arm.2
The SAS comprised 162 patients per arm; the FAS included 161 and 164 patients in the inavolisib and placebo arms, respectively. Sixty-two of 161 patients (38.5%) in the FAS of the inavolisib arm and 63 of 164 (38.4%) in the placebo arm were in North America or Western Europe; 58 of 161 (36.0%) and 62 of 164 (37.8%), respectively, in Asia; and 41 of 161 (25.5%) and 39 of 164 (23.8%), respectively, in other regions.2 Baseline disease characteristics were well balanced between arms; 132 of 161 (82.0%) and 128 of 164 (78.0%) patients had visceral disease.2 Median ages were 53.0 (range 27-77) and 54.5 years (29-79), and proportions of patients aged <65 years were 84.5% (136 of 161) and 79.3% (130 of 164) in the inavolisib and placebo arms, respectively.2
In the FAS at clinical cut-off, 58.4% of patients (94 of 161) discontinued inavolisib and 70.1% (115 of 164) discontinued placebo; 67 of 161 (41.6%) and 49 of 164 (29.9%) remained on treatment, respectively.2
Overall safety profile
Adverse events occurred in 160 of 162 (98.8%) patients in the inavolisib arm and in all patients in the placebo arm.2 The most common (by preferred term) in the inavolisib arm were neutropenia [88 of 162 (54.3%)], hyperglycaemia [87 of 162 (53.7%)], diarrhoea [78 of 162 (48.1%)], neutrophil count decreased [63 of 162 (38.9%)], anaemia [59 of 162 (36.4%)] and stomatitis [53 of 162 (32.7%)] (Table 1).
Table 1.
Adverse events occurring in ≥15% of patients in either treatment arm and grade 3-4 adverse events
| Patients, n (%) | Inavolisib + palbociclib + fulvestrant (n = 162) |
Placebo + palbociclib + fulvestrant (n = 162) |
||
|---|---|---|---|---|
| Any grade | Grade 3-4 | Any grade | Grade 3-4 | |
| Blood and lymphatic system disorders | ||||
| Neutropenia | 88 (54.3) | 77 (47.5) | 89 (54.9) | 78 (48.1) |
| Anaemia | 59 (36.4) | 10 (6.2) | 59 (36.4) | 3 (1.9) |
| Thrombocytopenia | 36 (22.2) | 8 (4.9) | 41 (25.3) | 3 (1.9) |
| Leukopenia | 28 (17.3) | 11 (6.8) | 40 (24.7) | 17 (10.5) |
| Investigations | ||||
| Neutrophil count decreased | 63 (38.9) | 56 (34.6) | 64 (39.5) | 53 (32.7) |
| Platelet count decreased | 42 (25.9) | 15 (9.3) | 36 (22.2) | 4 (2.5) |
| White blood cell count decreased | 35 (21.6) | 23 (14.2) | 35 (21.6) | 17 (10.5) |
| Aspartate aminotransferase increased | 28 (17.3) | 2 (1.2) | 26 (16.0) | 2 (1.2) |
| Alanine aminotransferase increased | 28 (17.3) | 6 (3.7) | 21 (13.0) | 2 (1.2) |
| Weight decreased | 28 (17.3) | 6 (3.7) | 1 (0.6) | 0 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 78 (48.1) | 6 (3.7) | 26 (16.0) | 0 |
| Stomatitis | 53 (32.7) | 5 (3.1) | 27 (16.7) | 0 |
| Nausea | 45 (27.8) | 1 (0.6) | 27 (16.7) | 0 |
| General disorders and administration site conditions | ||||
| Fatigue | 38 (23.5) | 0 | 21 (13.0) | 2 (1.2) |
| Asthenia | 25 (15.4) | 3 (1.9) | 22 (13.6) | 0 |
| Mucosal inflammation | 30 (18.5) | 3 (1.9) | 16 (9.9) | 0 |
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 87 (53.7) | 9 (5.6) | 12 (7.4) | 0 |
| Decreased appetite | 38 (23.5) | 0 | 14 (8.6) | 0 |
| Hypokalaemia | 26 (16.0) | 4 (2.5) | 10 (6.2) | 0 |
| Infections and infestations | ||||
| COVID-19 | 37 (22.8) | 3 (1.9) | 17 (10.5) | 1 (0.6) |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 26 (16.0) | 0 | 21 (13.0) | 0 |
| Alopecia | 30 (18.5) | 0 | 9 (5.6) | 0 |
| Nervous system disorders | ||||
| Headache | 34 (21.0) | 0 | 22 (13.6) | 0 |
Clinical cut-off for this analysis was 29 September 2023. Adverse events are preferred terms, not grouped terms.
Adverse event severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Grade 3-4 adverse events occurred in 143 of 162 (88.3%) patients in the inavolisib arm and 133 of 162 (82.1%) in the placebo arm.2 The most common (by preferred term) were neutropenia [77 of 162 (47.5%) and 78 of 162 (48.1%), respectively], neutrophil count decreased [56 of 162 (34.6%) and 53 of 162 (32.7%)] and white blood cell count decreased [23 of 162 (14.2%) and 17 of 162 (10.5%)] (Table 1).
Serious adverse events occurred in 39 of 162 (24.1%) patients in the inavolisib arm and 17 of 162 (10.5%) in the placebo arm.2 These were distributed across multiple preferred terms, and none had a ≥2% difference between arms.2
Grade 5 adverse events were reported in 6 of 162 (3.7%) patients in the inavolisib arm and 2 of 162 (1.2%) in the placebo arm.2 None were reported as related to any study drug by the investigator, and no preferred term was observed in >1 patient in either arm.
In the inavolisib arm, 112 of 162 (69.1%) patients had an inavolisib dose interruption due to an adverse event, 115 of 162 (71.0%) had a palbociclib dose interruption due to an adverse event and 52 of 162 (32.1%) had a fulvestrant dose interruption due to an adverse event. The median duration of inavolisib dose interruption was 1 day (range 1.0-64.0). Preferred terms for inavolisib dose interruptions in ≥10% of patients were hyperglycaemia [40 of 162 (24.7%)], COVID-19 [26 of 162 (16.0%)], neutropenia [20 of 162 (12.3%)] and neutrophil count decreased [17 of 162 (10.5%)].
In the inavolisib arm, 23 of 162 (14.2%) patients had an inavolisib dose reduction due to an adverse event, and 61 of 162 (37.7%) had a palbociclib dose reduction due to an adverse event. Preferred terms leading to inavolisib dose reductions in >2 patients were hyperglycaemia [4 of 162 (2.5%)] and stomatitis [3 of 162 (1.9%)].
Discontinuation rates due to adverse events were generally low. In the inavolisib arm, 10 of 162 (6.2%) patients discontinued inavolisib, 8 of 162 (4.9%) discontinued palbociclib and 5 of 162 (3.1%) discontinued fulvestrant.2 The only preferred term leading to withdrawal of any study drug in ≥2 patients was hyperglycaemia [inavolisib arm; 2 of 162 patients (1.2%)].
Subgroups
Tables 2 and 3 report an overview of safety by region (North America or Western Europe, Asia, and Other) and age [<65 years and ≥65 years; the ≥75-year group was excluded due to too few patients (five and six in the inavolisib and placebo arms, respectively)].
Table 2.
Safety overview by geographical region
| Geographical regionl patients with at least one: | Inavolisib + palbociclib + fulvestrant |
Placebo + palbociclib + fulvestrant |
||||
|---|---|---|---|---|---|---|
| Asia (n = 57) | North America/Western Europe (n = 63) | Other (n = 42) | Asia (n = 57) | North America/Western Europe (n = 63) | Other (n = 42) | |
| Any-grade adverse event, n (%) | 57 (100) | 63 (100) | 40 (95.2) | 57 (100) | 63 (100) | 42 (100) |
| Total number of adverse events, n | 1262 | 1369 | 667 | 693 | 905 | 460 |
| Treatment-related adverse event, n (%) | ||||||
| Inavolisib/placebo | 53 (93.0) | 58 (92.1) | 31 (73.8) | 44 (77.2) | 49 (77.8) | 23 (54.8) |
| Palbociclib | 55 (96.5) | 59 (93.7) | 38 (90.5) | 54 (94.7) | 61 (96.8) | 38 (90.5) |
| Fulvestrant | 28 (49.1) | 40 (63.5) | 16 (38.1) | 21 (36.8) | 41 (65.1) | 10 (23.8) |
| Any treatment | 57 (100) | 62 (98.4) | 39 (92.9) | 54 (94.7) | 61 (96.8) | 38 (90.5) |
| Grade 3-4 adverse event, n (%) | 55 (96.5) | 54 (85.7) | 34 (81.0) | 48 (84.2) | 53 (84.1) | 32 (76.2) |
| Grade 5 adverse event, n (%) | 2 (3.5) | 1 (1.6) | 3 (7.1) | 1 (1.8) | 0 | 1 (2.4) |
| Serious adverse event, n (%) | 16 (28.1) | 8 (12.7) | 15 (35.7) | 5 (8.8) | 6 (9.5) | 6 (14.3) |
| Adverse event leading to withdrawal from the study, n (%) | 1 (1.8) | 0 | 0 | 0 | 0 | 0 |
| Adverse event leading to withdrawal from treatment, n (%) | ||||||
| Inavolisib/placebo | 2 (3.5) | 6 (9.5) | 2 (4.8) | 0 | 1 (1.6) | 0 |
| Palbociclib | 3 (5.3) | 4 (6.3) | 1 (2.4) | 0 | 0 | 0 |
| Fulvestrant | 2 (3.5) | 2 (3.2) | 1 (2.4) | 0 | 0 | 0 |
| Any treatment | 3 (5.3) | 6 (9.5) | 2 (4.8) | 0 | 1 (1.6) | 0 |
| Adverse event leading to dose modification/interruption of treatment, n (%) | ||||||
| Inavolisib/placebo | 40 (70.2) | 45 (71.4) | 28 (66.7) | 15 (26.3) | 31 (49.2) | 11 (26.2) |
| Palbociclib | 51 (89.5) | 46 (73.0) | 28 (66.7) | 42 (73.7) | 47 (74.6) | 27 (64.3) |
| Fulvestrant | 14 (24.6) | 27 (42.9) | 11 (26.2) | 8 (14.0) | 18 (28.6) | 8 (19.0) |
| Any treatment | 52 (91.2) | 50 (79.4) | 32 (76.2) | 44 (77.2) | 48 (76.2) | 29 (69.0) |
Clinical cut-off for this analysis was 29 September 2023. Adverse event severity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Table 3.
Safety overview by age
| Age group; patients with at least one: | Inavolisib + palbociclib + fulvestrant |
Placebo + palbociclib + fulvestrant |
||
|---|---|---|---|---|
| <65 years (n = 138) | 65-74 years (n = 19) | <65 years (n = 128) | 65-74 years (n = 28) | |
| Any-grade adverse event, n (%) | 136 (98.6) | 19 (100) | 128 (100) | 28 (100) |
| Total number of adverse events, n | 2916 | 295 | 1654 | 359 |
| Treatment-related adverse event, n (%) | ||||
| Inavolisib/placebo | 121 (87.7) | 17 (89.5) | 90 (70.3) | 20 (71.4) |
| Palbociclib | 131 (94.9) | 17 (89.5) | 119 (93.0) | 28 (100) |
| Fulvestrant | 74 (53.6) | 9 (47.4) | 52 (40.6) | 17 (60.7) |
| Any treatment | 136 (98.6) | 18 (94.7) | 119 (93.0) | 28 (100) |
| Grade 3-4 adverse event, n (%) | 123 (89.1) | 16 (84.2) | 104 (81.2) | 23 (82.1) |
| Grade 5 adverse event, n (%) | 2 (1.4) | 2 (10.5) | 2 (1.6) | 0 |
| Serious adverse event, n (%) | 29 (21.0) | 7 (36.8) | 12 (9.4) | 4 (14.3) |
| Adverse event leading to withdrawal from the study, n (%) | 0 | 1 (5.3) | 0 | 0 |
| Adverse event leading to withdrawal from treatment, n (%) | ||||
| Inavolisib/placebo | 8 (5.8) | 2 (10.5) | 1 (0.8) | 0 |
| Palbociclib | 6 (4.3) | 2 (10.5) | 0 | 0 |
| Fulvestrant | 4 (2.9) | 1 (5.3) | 0 | 0 |
| Any treatment | 8 (5.8) | 3 (15.8) | 1 (0.8) | 0 |
| Adverse event leading to dose modification/interruption of treatment, n (%) | ||||
| Inavolisib/placebo | 94 (68.1) | 15 (78.9) | 41 (32.0) | 12 (42.9) |
| Palbociclib | 105 (76.1) | 16 (84.2) | 90 (70.3) | 20 (71.4) |
| Fulvestrant | 43 (31.2) | 6 (31.6) | 23 (18.0) | 9 (32.1) |
| Any treatment | 113 (81.9) | 17 (89.5) | 95 (74.2) | 20 (71.4) |
Clinical cut-off for this analysis was 29 September 2023.
Adverse event severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Key selected adverse events
Key selected adverse events by month of exposure and median duration of key selected adverse events in the inavolisib arm are shown in Figure 1A-E, respectively. Key selected events occurred within the first 30 days of therapy and were generally of short duration. Therefore, careful monitoring during the first cycle and adherence to management guidelines are highly recommended.
Figure 1.
(A-D) Key selected adverse events per month of exposurea and (E) median duration (range) of key selected adverse events in the inavolisib arm.baIf an adverse event was resolved and recurred in the same patient, it was not included a second time in this dataset. bDuration of adverse events was calculated using imputed start and end dates. The placebo arm, not shown as one of the study arms, is not comparable due to differences in patient populations.
A summary of key selected adverse event management strategies used is shown in the Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735.
Hyperglycaemia
In the SAS, approximately 40% of patients in the inavolisib (69 of 162) and placebo arms (66 of 162) had baseline risk factors for hyperglycaemia, including HbA1c ≥5.7% [16 of 162 (9.9%) and 21 of 162 (13.0%)], fasting glucose ≥100 mg/dL (5.6 mmol/L) [46 of 162 (28.4%) and 36 of 162 (22.2%)] and body mass index (BMI) ≥30 kg/m2 [29 of 162 (17.9%) and 28 of 162 (17.3%)].2 Sixteen of 162 (9.9%) and 20 of 162 (12.3%) met the American Diabetes Association prediabetes definition at baseline (HbA1c ≥5.7% to <6.5%) in the inavolisib and placebo arms, respectively.
Hyperglycaemia (grouped term) was reported in 58.6% of patients (95 of 162) in the inavolisib arm (per NCI-CTCAE v5.0); most events were grade 1 [26 of 162 (16.0%)] or grade 2 [60 of 162 (37.0%)]; 5.6% (9 of 162) experienced a grade 3 event; none experienced a serious or grade 4-5 event.2 The preferred terms ‘hyperglycaemia’ and ‘blood glucose increased’ were reported in 53.7% (87 of 162) and 4.9% (8 of 162), respectively. No patients had diabetic ketoacidosis. Among the inavolisib-treated patients who had hyperglycaemia events, median time to first onset was 7.0 days (range 2.0-955.0); median time to resolution was 16.0 days (interquartile range 5.0-50.0). In the 157 patients with a laboratory baseline fasting glucose value and ≥1 posttreatment value in the inavolisib arm, high postbaseline fasting glucose was classed as grade 1 using NCI-CTCAE v4.0 in 80 of 157 (51.0%); grade 2, in 35 of 157 (22.3%); grade 3, in 18 of 157 (11.5%); and grade 4, in one of 157 (0.6%) patients. For patients who experienced an increased fasting glucose of >160 mg/dL (8.9 mmol/L), 96.3% (52 of 54) had an improvement in fasting glucose of ≥1 grade level with a median time to improvement from the first event of 8 days (range 2-43).
Inavolisib dose interruptions, reductions and discontinuations due to hyperglycaemia were reported in 27.2% (44 of 162), 2.5% (4 of 162) and 0.6% (1 of 162) of patients, respectively. Of the 95 patients who had hyperglycaemia reported in the inavolisib arm, 75 (78.9%) reported an event as resolved and 20 (21.1%) did not have a resolved outcome by clinical cut-off (some patients were enrolled close to the cut-off date and adverse event follow-up is ongoing).
Of the 66 patients who received ≥1 concomitant medication for management (prophylaxis and adverse event treatment) of hyperglycaemia in the inavolisib arm, metformin, either as a single agent and in combination with other antihyperglycaemic agents, was the most common medication (62 of 66; 93.9%). Twelve of 162 patients (7.4%) received prophylactic metformin (defined as flagged by the investigator or as patients who started metformin on/before cycle 1, day 1). Eleven of 162 patients (6.8%) received insulin during the study; median duration was 5.0 days (range 1.0-539.0; the high upper range was due to two patients with chronic insulin use). No other concomitant medications for hyperglycaemia were reported in ≥5% of patients (Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735). In the inavolisib arm, 38 (23.5%), 19 (11.7%), 14 (8.6%) and 3 of 162 patients (1.9%) received one, two, three and four unique concomitant medications for hyperglycaemia. Hyperglycaemia incidence by risk factor at baseline is shown in Table 4.
Table 4.
Hyperglycaemia risk factor safety analyses
| Risk factor/number of risk factors | Inavolisib + palbociclib + fulvestrant (n = 162) |
||
|---|---|---|---|
| n | Patients with a hyperglycaemia event (any grade), n (%) | Patients with a hyperglycaemia event (grade 3–4), n (%)a | |
| Overall2 | 162 | 95 (58.6) | 9 (5.6) |
| BMI | |||
| <30 kg/m2 | 132 | 75 (56.8) | 4 (3.0) |
| ≥30 kg/m2 | 29 | 19 (65.5) | 5 (17.2) |
| Missing | 1 | 1 (100) | 0 |
| HbA1c | |||
| <5.7% | 145 | 87 (60.0) | 8 (5.5) |
| ≥5.7% | 16 | 7 (43.8) | 1 (6.2) |
| Missing | 1 | 1 (100) | 0 |
| Fasting blood glucose | |||
| <100 mg/dL (<5.6 mmol/L) | 112 | 59 (52.7) | 4 (3.6) |
| ≥100 mg/dL (≥5.6 mmol/L) | 46 | 34 (73.9) | 5 (10.9) |
| Missing | 4 | 2 (50.0) | 0 |
| Number of risk factors | |||
| 0 | 93 | 49 (52.7) | 2 (2.2) |
| 1 | 50 | 34 (68.0) | 4 (8.0) |
| 2 | 16 | 10 (62.5) | 2 (12.5) |
| 3 | 3 | 2 (66.7) | 1 (33.3) |
Clinical cut-off for this analysis was 29 September 2023.
Adverse event severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Percentages are based on the number of patients in each subgroup.
BMI, body mass index; HbA1c, glycated haemoglobin.
There were no grade 4 events.
Subgroups
In the prediabetic population enrolled in the inavolisib arm, 7 of 16 (43.8%) patients experienced any-grade hyperglycaemia [3 each at grade 1 and 2 (18.8%); 1 (6.3%) at grade 3], and none discontinued inavolisib due to hyperglycaemia. Metformin was the most common antihyperglycaemic used.
In the inavolisib arm, 36 of 57 (63.2%), 34 of 63 (54.0%) and 25 of 42 (59.5%) patients in Asia, North America or Western Europe, and Other regions, respectively, experienced hyperglycaemia, as did 82 of 138 (59.4%) and 10 of 19 (52.6%) patients aged <65 and 65-74 years, respectively.
Rash
Rash (grouped term) was reported in 41 of 162 (25.3%) patients in the inavolisib arm2; all events were nonserious and grade 1 [34 of 162 (21.0%)] or grade 2 [7 of 162 (4.3%)]; there were no grade 3-5 events. ‘Rash’ [26 of 162 (16.0%)] and ‘rash maculo-papular’ [7 of 162 (4.3%)] were the most common preferred terms. No severe cutaneous adverse reactions {e.g. Stevens–Johnson syndrome, erythema multiforme, toxic epidermal necrolysis or drug hypersensitivity syndrome [also known as drug rash with eosinophilia and systemic symptoms (DRESS)]} were reported.
Among the inavolisib-treated patients who had rash events, the median time to first onset was 29.0 days (range 1.0-952.0). Median time to resolution was 16.0 days (interquartile range 8.0-29.0). Of the 41 of 162 (25.3%) patients who experienced rash in the inavolisib arm, 35 of 41 (85.4%) reported an event as resolved.
Inavolisib dose interruptions, reductions and discontinuations due to rash were reported in 1.2% (2 of 162), 0.6% (1 of 162) and 0% (0 of 162) of patients, respectively.
Of the 26 patients who received ≥1 concomitant medication for rash in the inavolisib arm, the most common medications were topical hydrocortisone (5 of 26; 19.2%) and triamcinolone acetonide (4 of 26; 15.4%).
Subgroups
In the inavolisib arm, 15 of 57 (26.3%), 16 of 63 (25.4%) and 10 of 42 (23.8%) patients in Asia, North America or Western Europe, and Other regions, respectively, experienced rash, as did 39 of 138 (28.3%) and 2 of 19 (10.5%) patients aged <65 and 65-74 years, respectively.
Stomatitis/mucosal inflammation
Stomatitis/mucosal inflammation (grouped term) was reported in 83 of 162 (51.2%) patients in the inavolisib arm, mostly at grade 1 [52 of 162 (32.1%)] or grade 2 [22 of 162 (13.6%)]; 9 of 162 (5.6%) patients experienced a grade 3 event and none experienced a grade 4-5 event.2 ‘Stomatitis’ [53 of 162 (32.7%)] and ‘mucosal inflammation’ [30 of 162 (18.5%)] were the most common preferred terms.
Among the inavolisib-treated patients who had stomatitis/mucosal inflammation events, the median time to first onset was 13.0 days (range 1.0-610.0). Median time to resolution was 20.0 days (interquartile range 10.0-49.0). Of the 83 of 162 (51.2%) patients who experienced stomatitis/mucosal inflammation in the inavolisib arm, 68 of 83 (81.9%) reported an event as resolved.
Inavolisib dose interruptions, reductions, and discontinuations due to stomatitis/mucosal inflammation were reported in 9.9% (16 of 162), 3.7% (6 of 162) and 0.6% (1 of 162) of patients, respectively.
Of the 69 patients who received ≥1 concomitant medication for stomatitis/mucosal inflammation in the inavolisib arm, the most common medications were dexamethasone [31 of 69 (44.9%)], sodium bicarbonate [7 of 69 (10.1%)] and nystatin [7 of 69 (10.1%)] (Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735). The majority were used as topical formulations (mouthwash). Thirty-two of 162 patients (19.8%) in the inavolisib arm received prophylactic dexamethasone/triamcinolone mouthwash/topical formulations.
Subgroups
In the inavolisib arm, 35 of 57 (61.4%), 31 of 63 (49.2%) and 17 of 42 (40.5%) patients in Asia, North America or Western Europe and Other regions, respectively, experienced stomatitis/mucosal inflammation, as did 76 of 138 (55.1%) and 6 of 19 (31.6%) patients aged <65 and 65-74 years, respectively.
Diarrhoea
Diarrhoea was reported in 78 of 162 (48.1%) patients in the inavolisib arm2; most patients had grade 1 [45 of 162 (27.8%)] or grade 2 diarrhoea events [27 of 162 (16.7%)]. Grade 3 events were only reported in the inavolisib arm [6 of 162 (3.7%) patients], and no grade 4-5 events or colitis were reported in either arm. Two of 162 (1.2%) patients in the inavolisib arm experienced serious events2; both were grade 3 and were reported as recovered or resolved at clinical cut-off. One of the events was considered unrelated to any study drug, required treatment and lasted 7 days. The other was considered related to inavolisib only, did not require antidiarrhoeal treatment (intravenous hydration and electrolytes provided) and lasted 5 days.
Among the inavolisib-treated patients who had diarrhoea events, median time to first onset was 15.0 days (range 2.0-602.0); median time to resolution was 5.0 days (interquartile range 2.0-19.0). Of the 78 of 162 (48.1%) patients who experienced diarrhoea in the inavolisib arm, 68 of 78 (87.2%) reported an event as resolved.
Inavolisib dose interruptions, reductions and discontinuations due to diarrhoea were reported in 6.8% (11 of 162), 1.2% (2 of 162) and 0% (0 of 162) of patients, respectively. Of the 46 patients who received ≥1 concomitant medication for diarrhoea in the inavolisib arm, the most common medications were loperamide [33 of 46 (82.6%)] and diosmectite [6 of 46 (13.0%)] (Supplement, available at https://doi.org/10.1016/j.esmoop.2026.107735). No escalation treatment (e.g. steroids and opioids) was required in any patient.
Subgroups
In the inavolisib arm, 24 of 57 (42.1%), 37 of 63 (58.7%) and 17 of 42 (40.5%) patients in Asia, North America or Western Europe and Other regions, respectively, experienced diarrhoea, as did 70 of 138 (50.7%) and 7 of 19 (36.8%) aged <65 and 65-74 years, respectively.
Other selected adverse events
Ocular toxicities were reported in 36 of 162 (22.2%) patients in the inavolisib arm; all were grade 1-22 and nonserious; the most common toxicities were dry eye [14 of 162 (8.6%)], blurred vision [6 of 162 (3.7%)] and increased lacrimation [4 of 162 (2.5%)]. Ocular toxicity events did not lead to interruption, reduction or withdrawal of any study drug.
Pneumonitis (an overlapping toxicity with palbociclib) was reported in 3 of 162 (1.9%) patients in the inavolisib arm; all were grade 1-2 and nonserious. Pneumonitis led to inavolisib dose interruption in 1 of 162 (0.6%) patients but did not lead to dose reduction or withdrawal of any study drug.
Blood creatinine increased was reported in 9 of 162 (5.6%) patients in the inavolisib arm; one event was grade 3.
No treatment-emergent colitis was reported in the study.
Long-term safety
In the inavolisib arm, 69 of 162 (42.6%) patients received inavolisib treatment for at least 1 year at the clinical cut-off date of 2 February 2024. An overview of new-onset adverse events starting after 1 year of treatment in this population is reported in Table 5. No adverse events leading to withdrawal of study treatment occurred in the long-term safety population at the clinical cut-off date.
Table 5.
Long-term safety overview: new-onset adverse events reported only after 1 year on treatment, with at least 1 year on treatment with inavolisib/placebo + palbociclib + fulvestrant
| Patients with at least one: | Inavolisib + palbociclib + fulvestrant (n = 69) | Placebo + palbociclib + fulvestrant (n = 36) |
|---|---|---|
| Any-grade adverse event, n (%) | 57 (82.6) | 28 (77.8) |
| Total number of adverse events, n | 303 | 128 |
| Treatment-related adverse event, n (%) | ||
| Inavolisib/placebo | 34 (49.3) | 8 (22.2) |
| Palbociclib | 35 (50.7) | 10 (27.8) |
| Fulvestrant | 14 (20.3) | 4 (11.1) |
| Any treatment | 44 (63.8) | 13 (36.1) |
| Grade 3-4 adverse event, n (%) | 18 (26.1) | 5 (13.9) |
| Grade 5 adverse event, n (%) | 2 (2.9) | 0 |
| Serious adverse event, n (%) | 8 (11.6) | 2 (5.6) |
| Adverse event leading to withdrawal from treatment, n (%) | ||
| Inavolisib/placebo | 0 | 0 |
| Palbociclib | 0 | 0 |
| Fulvestrant | 0 | 0 |
| Any treatment | 0 | 0 |
| Adverse event leading to dose modification/interruption of treatment, n (%) | ||
| Inavolisib/placebo | 24 (34.8) | 7 (19.4) |
| Palbociclib | 25 (36.2) | 9 (25.0) |
| Fulvestrant | 13 (18.8) | 4 (11.1) |
| Any treatment | 28 (40.6) | 9 (25.0) |
Clinical cut-off date for this analysis was 2 February 2024.
Adverse event severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Further details on the long-term safety profile have been reported.9
Discussion
The inavolisib-based regimen had a safety profile consistent with the individual drugs and a low treatment discontinuation rate due to adverse events.2, 3, 4 Updated data with additional follow-up were consistent. Hyperglycaemia, rash, stomatitis/mucosal inflammation and diarrhoea were mostly low grade, manageable with protocol-recommended supportive measures and most resolved (reflected in the high dose intensity of each drug).2,4
The overall proportion of patients with ≥1 adverse event, events leading to inavolisib dose modification or interruption and events leading to study drug withdrawal were largely comparable across regions, supporting consistent manageability and tolerability of the inavolisib-based regimen. Fatal events were infrequent across regions, and serious events were mostly reported in the Other regions, followed by Asia and North America or Western Europe. There was a numerically higher incidence of grade 3-4 adverse events in Asia, compared with North America or Western Europe and Other regions. The proportion of patients experiencing hyperglycaemia and stomatitis/mucosal inflammation was numerically higher in Asia compared with Other regions. Proportions experiencing rash were consistent across regions, and diarrhoea was reported in a numerically higher proportion in North America or Western Europe than in Asia or Other regions.
Patients were relatively younger in INAVO120, as it recruited a first-line, poor-prognosis endocrine-resistant population. Adverse events leading to inavolisib dose interruption or modification and events leading to study drug withdrawal were largely comparable across age groups, supporting consistent manageability and tolerability of the inavolisib-based regimen. Overall, the proportions of serious adverse events and events leading to dose interruption or modification of any study treatment were numerically higher in patients aged 65-74 years compared with those aged <65 years, which could be due to a higher prevalence of comorbidities in elderly patients and/or a reduction in the reserve capacity of the organs in general.10 Fatal adverse events were rare across all age groups.
Hyperglycaemia, an on-target toxicity associated with PI3K pathway inhibitors, was more frequent in the inavolisib arm and occurred mostly in the first three treatment cycles, highlighting the importance of early, frequent fasting blood or plasma glucose monitoring and following hyperglycaemia management guidelines. Hyperglycaemia caused by inavolisib was an on-target effect that resolved upon treatment cessation, thereby eliminating the need for further antihyperglycaemic drugs (mostly metformin; a small number of patients received short-term insulin) in the majority of patients. Overall, hyperglycaemia was manageable and did not lead to a high proportion of patients needing inavolisib dose reductions or discontinuations.
The incidence of hyperglycaemia in the inavolisib arm was higher in patients with one, two or three risk factors, namely fasting glucose ≥100 mg/dL (≥5.6 mmol/L), HbA1c ≥5.7% and BMI ≥30 kg/m2 at baseline, compared with patients with none. INAVO120 excluded patients who had fasting glucose ≥126 mg/dL (≥7.0 mmol/L) and HbA1c ≥6.0% (originally ≥5.7%), and patients with type 1 and 2 diabetes on systemic therapy. GO39374 (NCT03006172), however, enrolled patients with HbA1c <7% and fasting glucose <140 mg/dL.11 GO39374 showed that in patients with risk factors for hyperglycaemia (HbA1c ≥5.7% and <6.5%; fasting glucose ≥100 mg/dL and <126 mg/dL; BMI ≥30 kg/m2), hyperglycaemia was frequent (81% of patients); inavolisib cumulative dose intensity was high (92%), with a low rate of discontinuation due to hyperglycaemia (1%); hyperglycaemia was manageable with dose interruptions (42%), reductions (14%) or oral antihyperglycaemic medications (64%) and was reversible (86%).12
Hyperglycaemia, being a known toxicity associated with PI3Kα inhibitors, has been reported with alpelisib13; however, cross-trial comparisons should be made with caution due to differences in trial design, patient populations, analysis, NCI-CTCAE versions used (4.0 in SOLAR-1 and 5.0 in INAVO120) and reporting.
Diarrhoea, stomatitis/mucosal inflammation and rash are commonly associated with PI3K pathway inhibitors; these were also more frequent in the inavolisib arm but were early-onset, low-grade, nonserious and manageable with supportive care and dose modifications. Prophylactic dexamethasone mouthwash was recommended for stomatitis based on the SWISH study7 and it was the most common concomitant medication. No prophylaxis for rash was recommended in INAVO120 based on the inavolisib mechanism of action (high α-selectivity) and data from the GO39374 study,11 whereas for alpelisib in SOLAR-1, prophylaxis with antihistamines was recommended.13
Ocular toxicities were mild, with dry eye and blurred vision being the most common ocular events reported. There were similar incidence rates of haematological adverse events across both arms for overall incidence and at grade 3 and 4 (with slightly higher rates of anaemia and thrombocytopenia), known CDK4/6 inhibitor-induced toxicities. The higher proportion of patients experiencing COVID-19 in the inavolisib arm may have been due to the longer time on study treatment, resulting in longer adverse event collection and observation period; median exposure to inavolisib was 9.2 months compared with 5.6 months for placebo.2 Specific starting dose adjustment guidance for patients with moderate–severe renal impairment is provided in the label.
The safety profile of inavolisib was consistent with that of long-term treated populations.9
The main limitation of the current analysis is the small subgroups. It should be noted in regional analyses that ‘Other’ comprised multiple regions with small patient numbers; therefore, interpretation should be made with caution. Differences in hyperglycaemia, stomatitis/mucosal inflammation and diarrhoea may also be related to compliance with management guidelines. Similarly, no meaningful conclusion can be made on the impact of HbA1c on hyperglycaemia incidence or on comparisons by age.
In summary, this analysis of INAVO120 demonstrates the generally consistent, manageable and tolerable safety profile of inavolisib in combination with palbociclib and fulvestrant. No new or unexpected safety signals were observed, and key selected adverse events that are commonly associated with PI3K inhibitors were generally nonserious, low-grade and mostly occurred in early treatment cycles (as such, focus should be on early monitoring, prevention and treatment). These events were generally reversible and were controlled with concomitant medications and dose modifications. Subgroup analyses showed numerical differences in certain adverse events, but they were manageable overall, and the long-term safety profile was consistent with previous reports. These analyses report a more detailed evaluation of the safety profile of inavolisib in combination with palbociclib and fulvestrant and provide guidance in adverse event management for patients receiving this regimen. This will help tailor the adverse event management and maximise the clinical benefit of inavolisib.
Acknowledgements
We thank all the patients who participated in INAVO120, along with their families, as well as the INAVO120 investigators and their research staff. The authors acknowledge the Memorial Sloan Kettering Cancer Center support grant (P30 CA008748). Sherene Loi is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. Research support in the form of third-party writing assistance for this manuscript, furnished by Kalina Boytcheva, MSc and Daniel Clyde, PhD, of Nucleus Global, an Inizio Company, was provided by F. Hoffmann-La Roche Ltd.
Funding
This work was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland (no grant number). The funder of the study had a role in study design, provision of study drugs, protocol development, regulatory and ethics approvals, safety monitoring, data collection, data analysis, data interpretation and writing of the report, in collaboration with the study authors.
Disclosure
All authors received research funding in the form of third-party medical writing support from F. Hoffmann-La Roche Ltd. S-AI received research grants from AstraZeneca, Boryung Corporation, Daewoong Pharmaceutical Company, Daiichi Sankyo Company, Eisai Korea, F. Hoffmann-La Roche AG, Pfizer and Entity (all to institution); served as an advisory board member for AstraZeneca, BERTIS, Daiichi Sankyo Company, Eisai, Eli Lilly and Company, GlaxoSmithKline, Hanmi Pharmaceutical Co., Idience Co. Ltd, MSD Korea, Novartis and Pfizer; and in a consultancy role for F. Hoffmann-La Roche Ltd. KK served in a consultancy role for AstraZeneca, Biotheranostics, eFFECTOR Therapeutics, Eisai, Eli Lilly and Company, Genentech, Inc., Gilead Sciences, Inc., Immunomedics, Ipsen Biopharmaceuticals, Inc., Mersana Therapeutics, Novartis, Pfizer, Prelude Therapeutics, Puma Biotechnology, Inc., RayzeBio, Relay Therapeutics, Seattle Genetics and Takeda Oncology; and received speakers’ bureau honoraria from Eli Lilly and Company, as well as grants/contracts from F. Hoffmann-La Roche Ltd (to institution); he is a Steering Committee member for Genentech, Inc. and Immunomedics. KLJ has served as a consultant/in an advisory board role for Novartis, Pfizer, Genentech, Inc., AbbVie, Eisai, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Menarini/Stemline, Gilead, Scorpion Therapeutics, Olema Pharmaceuticals, Bicycle Therapeutics, Eli Lilly/Loxo Oncology and Zymeworks. He has received research funding from Novartis, Genentech, Inc., AstraZeneca, Pfizer, Eli Lilly/Loxo Oncology, Zymeworks, Immunomedics/Gilead, Puma Biotechnology, Merck Pharmaceuticals, Scorpion Therapeutics, Eisai, RayzeBio and Blueprint Medicines (all to institution). SLoibl has received clinical trial research funding from F. Hoffmann-La Roche Ltd, AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo Company and Greenwich Biosciences, Inc. (to institution); honoraria for lectures and advisory boards from AbbVie, Amgen, AstraZeneca, Celgene, Merck, Novartis, Pfizer, Pierre Fabre Pharmaceuticals, Inc., Samsung and Seattle Genetics (to institution); adviser honoraria from Bristol Myers Squibb (to institution); lectures from Chugai Pharmaceutical; honoraria from Daiichi Sankyo Company (to institution); and is an adviser for studies for Eirgenix; has received clinical trial grants from Fondazione Internazionale Menarini, Immunomedics, Inc., Novartis and Pfizer (to institution); honoraria for advisory boards from Lilly Deutschland (to institution); translational research grants from Molecular Health (to institution); serves as an advisory board member for Olema and Relay Therapeutics; has received honoraria for lectures from PRIME SURGICAL, LLC (to institution); is an adviser for Sanofi; and has applied for the following patents (EP14153692.0, EP14153692.0, EP21152186.9, EP19808852.8, EP15702464.7 [all pending and held by institution]). NT receives clinical research grants from AstraZeneca, F. Hoffmann-La Roche Ltd, Guardant, Inivata, Merck Sharp & Dohme, Natera, Personalis and Pfizer, Inc. (all to institution); is an advisory board member for AstraZeneca, Eli Lilly, Exact Sciences, Genentech, Inc., Gilead Sciences (aka Gilead Foundation), GlaxoSmithKline, Guardant, Invitae, Novartis, Pfizer, Inc., Relay Therapeutics and Repare Therapeutics. CSaura reports consulting fees, honoraria, or meeting/travel support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Genentech, Inc., Gilead, Eli Lilly, MediTech, Menarini, MSD Spain, Novartis, Pfizer, Philips Healthcare, Pharmalex, Pierre Fabre, Puma Biotechnology, Roche, Seagen, Synthon and Zymeworks. CSaura is furthermore a member of the SOLTI Executive Board and Scientific Committee. PS has received research grant/funding from Astellas Pharma, AstraZeneca, F. Hoffmann-La Roche Ltd, Genentech, Inc., Medivation, Inc., Novartis and OncoGenex Pharmaceuticals, Inc. (to institution); serves in a consultancy role for AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, F. Hoffmann-La Roche Ltd, Merck, Pfizer and Puma Biotechnology; carries out data and safety monitoring for Novartis; and received honoraria from Novartis and Puma Biotechnology. SLoi receives research funding from Novartis, Bristol Myers Squibb, AstraZeneca/Daiichi Sankyo, Roche-Genentech, MSD, Pfizer, Gilead Sciences, Nektar Therapeutics and Eli Lilly (all to institution); is a consultant for Roche-Genentech, MSD, Gilead Sciences, AstraZeneca/Daiichi Sankyo, Bristol Myers Squibb, Novartis, Eli Lilly, Amaroq Therapeutics, Mersana Therapeutics, Domain Therapeutics, BioNTech, Bicycle Therapeutics, Exact Sciences, Menari Asia-Pacific, SAGA Diagnostics and Adanate; and receives speakers’ bureau honoraria from Novartis, MSD, Gilead, Exact Sciences, Roche-Genentech and AstraZeneca. EH received research funding from AbbVie, Acerta Pharma, Accutar Biotechnology, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, BeiGene, Black Diamond, Bliss BioPharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Cascadian Therapeutics, Clovis, Compugen, Context Therapeutics, Cullinan, Curis, CytomX, Daiichi Sankyo, Dana-Farber Cancer Institute, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Eisai, Ellipses Pharma, Elucida Oncology, EMD Serono, Fochon Pharmaceuticals, FujiFilm, G1 Therapeutics, Gilead Sciences, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, Infinity Pharmaceuticals, Inspirna, InventisBio, Jacobio, Karyopharm, K-Group Beta, Kind Pharmaceuticals, Leap Therapeutics, Eli Lilly, Loxo Oncology, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Mersana, Merus, Millennium, Molecular Templates, Myriad Genetic Laboratories, Novartis, Nucana, Olema, OncoMed, Oncothyreon, ORIC Pharmaceuticals, Orinove, Orum Therapeutics, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Prelude Therapeutics, Profound Bio, Radius Health, Regeneron, Relay Therapeutics, Repertoire Immune Medicine, Rgenix, Roche/Genentech, Seagen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback Therapeutics, StemCentRx, Stemline Therapeutics, Sutro, Syndax, Syros, Taiho, TapImmune, Tesaro, Tolmar, Torque Therapeutics, Treadwell Therapeutics, Verastem, Zenith Epigenetics and Zymeworks (all to institution); serves in consulting/advisory roles for Accutar Biotechnology, Arvinas, AstraZeneca, Circle Pharma, Daiichi Sankyo, Entos, Gilead Sciences, IQVIA, Janssen, Jazz Pharmaceuticals, Jefferies LLC, Johnson & Johnson, Eli Lilly, Medical Pharma Services, Mersana Therapeutics, Olema Pharmaceuticals, Pfizer, Roche/Genentech, Shorla Pharma, Stemline Therapeutics, Tempus Labs, Theratechnologies, Tubulis and Zentalis Pharmaceuticals (all to institution). NK has no conflicts of interest to disclose. SW reports consultant or advisory roles for AstraZeneca and Daiichi Sankyo; has acted as a speaker for AstraZeneca, Eli Lilly, Novartis, Pfizer and Roche; and has received research funding from AstraZeneca and Pfizer. AAA serves in consultancy roles for AstraZeneca, Eli Lilly, Exact Sciences, Exactis, Gilead, Knight Therapeutics, Novartis, Pfizer and Roche; has received honoraria from Apotex/Apobiologix, AstraZeneca, Eli Lilly and Roche; has received funding for clinical trials from Astellas, AstraZeneca, Canexia Health, Exactis, Intensity Therapeutics, Pfizer, Roche, Roche Diagnostics, Seagen and Sermonix (all to institution). EMC reports institutional research grants from Roche, Seagen and Daiichi Sankyo; consulting fees from Roche, Eli Lilly, Pfizer, Novartis, Daiichi Sankyo, AstraZeneca, MSD and Menarini; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Roche, Eli Lilly and Novartis; support for attending meetings and/or travel from Roche, AstraZeneca and Pfizer; and participation on a Data Safety Monitoring Board or advisory board for Roche, Eli Lilly, Pfizer, Novartis, Daiichi Sankyo, AstraZeneca, MSD, Menarini and Reveal Genomics. C-FC serves on advisory boards for Daiichi Sankyo, Roche, AstraZeneca, Novartis, Pfizer and MSD; and has been an invited speaker for Daiichi Sankyo, Roche, AstraZeneca, Eli Lilly, Novartis, Pfizer and MSD. ET was employed by Roche Products Limited; and had stock options in F. Hoffmann-La Roche Ltd at the time of writing; and holds the following patent (18208024). NS is employed by Genentech, Inc.; and holds stock options in F. Hoffmann-La Roche Ltd. SLim is employed by Genentech, Inc.; and holds stock options in F. Hoffmann-La Roche Ltd. YJ is employed by Hoffmann-La Roche Limited; and holds stock options in F. Hoffmann-La Roche Ltd. CSong is employed by Genentech, Inc.; and has stock options in F. Hoffmann-La Roche Ltd. DJ has clinical trial contracts with Amgen, Inc., AstraZeneca, Blueprint Medicines Corporation, EISAI INC., Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Genentech, Inc., Infinity Pharmaceuticals, Novartis, Pfizer, Ribon Therapeutics, Seagen, Inc., Syros Pharmaceuticals and Takeda Oncology (all to institution); serves as a scientific advisory board member for AstraZeneca, EISAI INC., Eli Lilly and Company, Genentech, Inc., Mapkure, Novartis, Relay Therapeutics, Syros Pharmaceuticals and Vibliome; and in a consultancy role for Pfizer; and has received grants/contracts from Scorpion Therapeutics (to institution).
Data Availability
Qualified researchers may request access to individual patient-level data through the clinical study data request platform: https://vivli.org/. Further details on Roche’s criteria for eligible studies are available here: https://vivli.org/members/ourmembers/. For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm.
Supplementary data
References
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