Clinical outcomes of patients with PIK3CA mutations in circulating tumor DNA: update from the MONARCH 2 study of abemaciclib plus fulvestrant

Goal To assess overall survival (OS), time to chemotherapy (TTC) and chemotherapy-free survival (CFS) in patients with and without PIK3CA mutations in MONARCH 2.

Material and method MONARCH 2 was a global, randomized, double-blind phase III trial of abemaciclib+fulvestrant or placebo+fulvestrant in pre-/perimenopausal (with ovarian suppression) and postmenopausal women with endocrine therapy resistant HR+, HER2- advanced breast cancer. Results of PIK3CA mutation status (E542K; E545K; H1047L; H1047R) from baseline ctDNA were available for 238 patients. Exploratory analyses of OS, TTC and CFS were assessed in patients with/without PIK3CA mutations using Cox Regression Models with treatment, PIK3CA mutation status and treatment by PIK3CA interaction term as covariates.

Results Abemaciclib+fulvestrant demonstrated a similar OS benefit in PIK3CA mutant (hazard ratio [HR]: 0.57; 95 % confidence interval [CI]: 0.34, 0.96) and PIK3CA wild-type (HR: 0.56; 95 %CI: 0.34, 0.91) versus placebo+fulvestrant. TTC was longer for abemaciclib+fulvestrant versus placebo+fulvestrant both in PIK3CA mutant (HR: 0.65; 95 %CI: 0.37, 1.18) and PIK3CA wild-type (HR: 0.50; 95 %CI: 0.31, 0.78). CFS was also longer for abemaciclib+fulvestrant versus placebo+fulvestrant both in PIK3CA mutant (HR: 0.63; 95 %CI: 0.39, 1.03) and PIK3CA wild-type (HR: 0.53; 95 %CI: 0.35, 0.80).

Summary In this exploratory analysis of MONARCH 2, abemaciclib+fulvestrant demonstrated benefit in OS, TTC and CFS in patients with and without PIK3CA mutations.

Interessenkonflikt

Sara Tolaney Institutional Research Funds; honorarium; travel expense reimbursement - AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Bristol-Myers Squibb, Eisai, Nanostring Institutional Research Funds - Exelixis, Cyclacel Honorarium; travel expense reimbursement- Puma, Celldex Honorarium- Sanofi, Paxman, Seattle Genetics Masakazu Toi Honoraria - AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Genomic Health; Konica Minolta; Kyowa Hakko Kirin; Lilly; Novartis; Pfizer; Shimadzu; Taiho Pharmaceutical; TAKEDA; Yakult Pharmaceutical Consulting or Advisory Role - Daiichi Sankyo; Konica Minolta; Kyowa Hakko Kirin Speakers´ Bureau - AstraZeneca; Lilly; Pfizer Research Funding - AFI technology; Astellas Pharma; AstraZeneca; Chugai Pharma; Daiichi Sankyo; Eisai; Japan Breast Cancer Research Group; Kyoto Breast cancer Research Network; Nippon Kayaku; Ono Pharmaceutical; Pfizer; Shimadzu; Taiho Pharmaceutical Patents, Royalties, Other Intellectual Property - JP 2017-143763 WO2017/131162A1 (Inst); PCT/JP2016/004374 (Inst) Travel, Accommodations, Expenses - Eisai; Takeda Other Relationship - Japan Breast Cancer Research Group; Japan Breast Cancer Research Group; Kyoto Breast Cancer Research Network; Organization for Oncology and Translational Research Patrick Neven Honoraria - Lilly (Inst) Consulting or Advisory Role - Lilly (Inst); Novartis (Inst); Pfizer (Inst); Roche (Inst) Research Funding - Kom op tegen Kanker Joohyuk Sohn Research Funding - AstraZeneca (Inst); Bayer (Inst); Daiichi Sankyo (Inst); GlaxoSmithKline (Inst); Lilly (Inst); MSD (Inst); Novartis (Inst); Pfizer (Inst); Roche (Inst Eva-Maria Grischke, Reisekostenunterstützungen, Honorare Hatem Soliman Consulting: AstraZeneca, Celgene, Novartis, Eisai Lacey M. Litchfield Employment - Lilly Stock and Other Ownership Interests - Lilly Hong Wang Employment - Lilly Stock and Other Ownership Interests - Lilly Sameera Wijayawardana Employment - Lilly Stock and Other Ownership Interests - Lilly Valerie M. Jansen Employment - Mersana Therapeutics Stock and Other Ownership Interests – Lilly, Mersana Therapeutics George W. Sledge, Jr Leadership - Syndax; Tessa Therapeutics Stock and Other Ownership Interests - Syndax; Tessa Therapeutics Consulting or Advisory Role - Radius Health; Symphogen; Synaffix; Syndax; Taiho Pharmaceutical; Verseau Therapeutics Research Funding - Genentech/Roche (Inst); Pfizer (Inst) Travel, Accommodations, Expenses - Radius Health; Tessa Therapeutics; Verseau Therapeutics

Publication History

Article published online:
01 June 2021