392P - Quality-adjusted time without symptoms of disease progression or toxicity of treatment (Q-TWiST) analysis to assess benefit-risk of sacituzumab govitecan (SG) in previously treated patients (pts) with metastatic triple-negative breast cancer (mTNBC)

Background

The phase 3 ASCENT trial included previously treated pts with mTNBC and demonstrated significantly prolonged overall and progression-free survival for SG vs chemotherapy treatment of physician’s choice (TPC). Rate of treatment emergent adverse events (TEAEs) was similar in SG and TPC arms. The objective of this analysis was to assess benefit and risk of SG vs TPC while accounting for pt quality of life in ASCENT.

Methods

Q-TWiST analysis was used to compare SG vs TPC. Survival time was partitioned into 3 health states: 1) with toxicity (TEAE ≥ 3) before disease progression until the earliest of TEAE being resolved, disease progression, death, or end of follow-up; 2) without toxicity before disease progression; and 3) disease progression until death or end of follow-up, whichever was first. Health state utilities were derived from published literature. A sensitivity analysis was performed with TEAE ≥ 2. Q-TWiST was calculated as utility-weighted sum of mean health state durations. Differences in Q-TWiST and relative Q-TWiST gains were assessed. Relationship between pt follow-up time vs Q-TWiST gain and difference in time spent in toxicity (SG vs TPC) was determined. The established threshold for relative Q-TWiST gain considered clinically important is 10% and clearly clinically important 15%.

Results

SG had significantly longer Q-TWiST (8.3 months [mo]; 95% CI, 7.6-9.1) than TPC (4.8 mo; 95% CI, 4.3-5.4) in pts with mTNBC, a difference of 3.5 mo (95% CI, 2.6-4.4; P <. 0001). Relative Q-TWiST improvement with SG was 39.5%. Q-TWiST benefits of SG over TPC increased with longer follow-up to week 138. Restricted mean time with toxicity was numerically higher with SG vs TPC, remaining stable with longer follow-up. In the sensitivity analysis SG had significantly longer median Q-TWiST vs TPC (difference 3.3 mo (95% CI, 2.3-4.1; P <. 0001) and relative Q-TWiST improvement was 36.5%.

Conclusions

SG demonstrated statistically significant and clearly clinically meaningful improvement in Q-TWiST compared to TPC in pts with previously treated mTNBC. Net benefits of SG continued to accrue with longer follow-up.

Clinical trial identification

NCT02574455.

Editorial acknowledgement

Medical writing and editorial support was provided by Ben Labbe, PhD, of Parexel.

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

A.M. Brufsky: Financial Interests, Personal, Advisory Board: Gilead, Astrazeneca, Novartis, Lilly, Pfizer, Daiichi Sankyo, Roche/Genentech, Puma, Eisai, Merck; Financial Interests, Personal, Other, Consultant: Sanofi, General Electric; Financial Interests, Institutional, Local PI: Astrazeneca, Daiichi Sankyo, Lilly, Roche/Genetech; Financial Interests, Institutional, Steering Committee Member: Gilead, Puma. 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, Coordinating PI: 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. M.S. Sedrak: Financial Interests, Institutional, Coordinating PI, Eli Lilly investigator-initiated trial: Eli Lilly. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Lilly, Pierre Fabre, Roche, Seagen, Abbvie, Sanofi, Gilead, Merck, Novartis, Relay Therapeutics; Financial Interests, Institutional, Invited Speaker: AstraZeneca, DSI, Novartis, Pfizer, Roche, Gilead, Seagen, Stemline-Menarini; Financial Interests, Institutional, Advisory Board: Pfizer, Olema; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Advisory Board, Ki67 Quantifier: VMscope GmbH; Financial Interests, Institutional, Research Grant: AstraZeneca, Celgene, Novartis, Immunomedics/Gilead, Pfizer, Roche, Daiichi Sankyo; Financial Interests, Institutional, Funding: AbbVie, Molecular Health, Greenwich Life Sciences; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics/Gilead; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Personal, Other, SC Capitello; EC Cambria 1: AstraZeneca; Financial Interests, Personal, Other, SC Inavo: Roche; Financial Interests, Personal, Other, SC Destiny B05; SC Destiny B09: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Advisory Role, Group in Germany responsible for breast cancer guidelines: AGO Kommission Mamma; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Member guideline committee; past chair in ESMO Breast: ESMO; Other, EP14153692.0No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP19808852.8 No financial interest, Institutional: Patent. 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