Abstract 189P
Background
SG is a Trop-2–directed antibody-drug conjugate (ADC) approved in multiple countries for the treatment of relapsed or refractory mTNBC. In the phase III ASCENT study (n = 529), significantly longer PFS (hazard ratio [HR], 0.43; 95% CI, 0.35-0.54), and OS (HR, 0.51; 95% CI, 0.41-0.62) were observed with SG vs chemotherapy treatment of physician’s choice (TPC), as of the data cutoff date of Mar 11, 2020 (median follow-up of 17.7 months). The incidence of obesity has grown to epidemic proportions in recent decades, and it is unclear what impact this may have on treatment outcomes especially for ADCs like SG which have weight-based dosing. Here, we look at the safety and efficacy of SG vs TPC among BMI subgroups.
Methods
This ad hoc subgroup analysis included pts from the full intent-to-treat population of ASCENT who received SG at 10 mg/kg of body weight or TPC. BMI was assessed at baseline and was classified as follows: underweight/normal (< 25 kg/m2), overweight (25 - < 30 kg/m2), and obese (≥ 30 kg/m2).
Results
As of Feb 25, 2021, longer PFS and OS, and higher ORR were observed with SG compared with TPC in pts from all BMI subgroups (Table). Grade ≥ 3 treatment-emergent adverse events (TEAEs) were observed in 68%, 78%, and 77% of pts treated with SG in the underweight/normal, overweight, and obese subgroups, respectively. TEAEs leading to dose reductions were observed in 11%, 24%, and 41% of pts, respectively, and TEAEs leading to treatment discontinuation were observed in 4%, 3%, and 8%, respectively. Table: 189P
| Underweight/Normal(< 25 kg/m2)46% | Overweight(25 - < 30 kg/m2)29% | Obese(≥ 30 kg/m2)25% | ||||
| SG n = 127 | TPC n = 114 | SG n = 71 | TPC n = 84 | SG n = 68 | TPC n = 64 | |
| Median PFS, a mo | 4.2 | 1.9 | 4.6 | 1.5 | 5.9 | 2.6 |
| (95% CI) | (2.9-5.6) | (1.5-2.8) | (3.3-6.3) | (1.4-1.6) | (4.1-8.3) | (1.6-3.0) |
| HR | 0.5 | 0.31 | 0.34 | |||
| (95% CI) | (0.37-0.69) | (0.20-0.47) | (0.21-0.53) | |||
| Median OS, mo | 10.9 | 6.2 | 10.8 | 6.7 | 14.9 | 8.7 |
| (95% CI) | (9.4-13.0) | (4.8-7.1) | (9.0-14.2) | (5.2-8.9) | (11.2-16.8) | (6.7-9.8) |
| HR | 0.55 | 0.51 | 0.45 | |||
| (95% CI) | (0.42-0.74) | (0.35-0.74) | (0.30-0.67) | |||
| ORR,a % | 25.2 | 7.9 | 33.8 | 1.2 | 39.7 | 1.6 |
| (95% CI) | (17.9-33.7) | (3.7-14.5) | (23.0-46.0) | (0.0-6.5) | (28.0-52.3) | (0.0-8.4) |
aIndependent review.ORR, objective response rate; OS, overall survival; PFS, progression-free survival.
Conclusions
To our knowledge, this is the first study evaluating the impact of BMI on treatment with ADCs. SG demonstrated improved efficacy vs TPC and a manageable safety profile in all evaluated BMI subgroups from ASCENT. Although a larger proportion of pts with high BMI (especially obese pts) had SG dose reduction, this did not translate into a decrease in efficacy.
Clinical trial identification
NCT02574455.
Editorial acknowledgement
Medical writing and editorial support was provided by Sonal S. Joshi, PhD, of Parexel.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
L. García Estevez: Financial Interests, Personal, Invited Speaker, Oncologist Meeting: Gilead, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Breast Cancer Advisory Board: MSD; Financial Interests, Personal, Invited Speaker, Breast Cancer Preceptorship: MSD; Financial Interests, Institutional, Invited Speaker, Obesity and metabolism in breast cancer: Roche. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly, Menarini; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. H.S. Rugo: Financial Interests, Personal, Other, Consultancy/advisory support: NAPO, Mylan/Viatris, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Daiichi Sankyo, AstraZeneca, Gilead Sciences, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. L.A. Carey: Financial Interests, Institutional, Other, DSMB: Novartis, Roche; Financial Interests, Institutional, Research Grant, research funding: Nanostring Technologies, Veracyte; Financial Interests, Institutional, Funding, research funding: Seagen; Financial Interests, Institutional, Invited Speaker, research funding: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Other, DSMB, steering committee: Lilly; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Sanofi, Novartis, Genentech/Roche, GSK, AstraZeneca/ Daiichi Sankyo; Non-Financial Interests, Advisory Role: Lilly. V.C. Dieras: Financial Interests, Personal, Advisory Board, National advisory board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board, Steering Committee, consultant, Symposium, travel expenses: Roche Genentech; Financial Interests, Personal, Advisory Board, + Symposia and travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Advisory boards, symposia, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, symposia, travel expenses: Seagen, Gilead; Financial Interests, Personal, Advisory Board, Steering Committee: AbbVie; Financial Interests, Personal, Advisory Board: Eisai, Medac GmbH; Financial Interests, Personal, Other, IDMC: Sanofi; Financial Interests, Personal, Advisory Board, national board: Menarini; Financial Interests, Personal and Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Invited Speaker: Roche Genentech, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee: Lilly; Financial Interests, Institutional, Invited Speaker, + IDMC: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, PI: Seagen. 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