216MO - A randomized phase II trial of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) vs weekly paclitaxel (P) as first- or second-line treatment in patients (pts) with ER+/HER2- metastatic breast cancer (MBC): The METEORA-II trial (IBCSG 54-16)

Background

METEORA-II was designed to test the concept of the metronomic VEX regimen administered for as long as the pt has the possibility of deriving a benefit from it, in comparison with weekly P, for pts with ER+/HER2- MBC candidates for chemotherapy (CT). Time to treatment failure (TTF) was chosen as primary endpoint, as CT may be stopped due to lack of tolerability, lack of efficacy or pt preference.

Methods

From Sept 2017 to Jan 2021, 140 pts were randomized at 15 centers in Italy, 133 initiated VEX (n=70) or P (n=63) in 4-week cycles and entered the efficacy analysis population. CT could be delayed by a maximum of 3 weeks. TTF was defined from randomization until permanent discontinuation of P or at least 1 VEX agent for any reason, or censored at date of last dose. A total of 123 TTF events had 80% power to detect HR=0.60 (median TTF from 4.5 to 7.5 months with VEX; α=0.05). At final analysis, 128/133 pts had experienced TTF events and 61 pts had died. Median follow-up was 29 months.

Results

The 133 pts with ER+/HER2- MBC had median age 61 years (30-80); 21% were ECOG PS 1, 78% had measurable disease. In total, 16% of pts had prior CT for MBC; 56% had only prior ET for MBC usually with CDK4/6 inhibitor (47%). VEX significantly improved TTF compared with P (HR=0.61; 95% CI 0.42-0.88; p=0.008). The median TTF was 8.3 vs 5.7 months (VEX vs P) and the 12-month TTF was 34.3 vs 8.6%. The median PFS was 11.1 vs 6.9 months favoring VEX (HR=0.67; 95% CI 0.46-0.96, p=0.03). The 12-months PFS was 43.5% vs. 21.9 % (VEX vs P). There was no difference in OS (HR=0.98; 95% CI 0.59-1.63). For 56% of pts, the TTF event was progression of disease; for 23% of pts, it was AE(s). More pts assigned VEX had at least 1 grade 3+ targeted AE (42.9%; 95% CI 31.1-55.3% vs 28.6%; 95% CI 17.9-41.3); neutrophil count decrease was the most frequent grade 4 AE (9/70 VEX and 1/63 P). Three pts died during treatment (1 P; 2 VEX).

Conclusions

METEORA-II trial showed VEX significantly improved TTF compared with P. VEX metronomic oral treatment should be considered as a first-line CT regimen for pts with ER+/HER2- MBC that require CT.

Clinical trial identification

NCT02954055 EudraCT Number: 2016-002200-39.

Editorial acknowledgement

Legal entity responsible for the study

ETOP IBCSG Partners Foundation.

Funding

ETOP IBCSG Partners Foundation.

Disclosure

E. Munzone: Financial Interests, Personal, Advisory Role: Eisai, Exact Sciences, MSD Oncology, Daiichi Sankyo/AstraZeneca, Pfizer, Seagen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, Lilly, Novartis. M.M. Regan: Financial Interests, Personal, Advisory Board, Also invited speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Includes consulting.: Tolmar Pharmaceuticals; Financial Interests, Personal, Invited Speaker: WebMD; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, Bayer; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial supported by company: Novartis; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported by company: Pfizer, Ipsen, TerSera; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial drug supply from company: Roche; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported or drug supply from company: AstraZeneca; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials with funding from company: Debiopharm; Non-Financial Interests, Advisory Role: Bristol-Myers Squibb. E. Montagna: Financial Interests, Personal, Advisory Role: Novartis, Pierre Fabre. L. Gianni: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expense: Novartis, Pfizer, Roche, Daiichi Sankyo/AstraZeneca; Financial Interests, Institutional, Funding, research funding to my Institution: Tesaro, Roche, AstraZeneca, SeattleGenetics, Puma Biotechnology; Non-Financial Interests, Member, Olympia Steering Committee: AstraZeneca. U.F.F. De Giorgi: Financial Interests, Personal, Advisory Board: Pfizer, BMS, MSD, Pharmamar, Astellas, Bayer, Ipsen, Novartis; Financial Interests, Personal, Invited Speaker: Roche, BMS, Sanofi, Astrazeneca; Financial Interests, Institutional, Research Grant: Astrazeneca, Sanofi, Roche. D. Generali: Financial Interests, Personal, Advisory Role: Novartis, Lilly, Pfizer, AstraZeneca, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Pfizer, Roche. F. Puglisi: Financial Interests, Institutional, Research Grant, Disclosure is outside the submitted work: AstraZeneca, Eisai, Roche; Financial Interests, Personal, Other, Honoraria or consultation fees / Disclosure is outside the submitted work: Amgen, AstraZeneca, Daichii Sankyo, Celgene, Eisai, Gilead, GSK, Ipsen, MSD, Novartis, Pierre Fabre, Pfizer, Seagen, Takeda, Viatris; Financial Interests, Personal, Officer, Honoraria or consultation fees / Disclosure is outside the submitted work: Eli Lilly; Financial Interests, Personal, Other, Honoraria or consultation fees / Disclosure is outside the submitted wor: Roche. C. Zamagni: Financial Interests, Personal, Advisory Board: Roche, Eisai, Novartis, AstraZeneca, Pfizer, PharmaMar, Amgen, Tesaro, QuintilesIMS, Lilly, Celgene; Financial Interests, Personal, Other, travel accommodation: Roche, Novartis, PharmaMar, Tesaro, PierreFabre, Istituto Gentili, Celgene; Financial Interests, Personal, Officer, travel accommodation: Pfizer; Financial Interests, Institutional, Funding, research funding to institution: Roche, Novartis, AstraZeneca, Pfizer, SeattleGenetics, Tesaro, PierreFabre, Istituto Gentili, Takeda, Teva, Medivation, AbbVie, Array BioPharma, Morphotek, Synthon; Non-Financial Interests, Member, Member of scientific committee of patients non-profit organization: Europa Donna Italy, Susan J Komen Emilia-Romagna, LOTO Onlus, Mamazone Sudtirol. M.A. Colleoni: Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Institutional, Leadership Role, Co-Chair Scientific Committee IBCSG: IBCSG. All other authors have declared no conflicts of interest.