LBA20 - First-line carboplatin-cyclophosphamide (CC) versus paclitaxel (P) with or without atezolizumab (atezo) for metastatic triple negative breast cancer (mTNBC): Results from a multicenter, randomized phase IIb trial: The Triple-B study (BOOG 2013-01)

Background

The addition of programmed cell death protein 1 (PD1) blockade to chemotherapy (CT) has improved survival for patients (pts) with mTNBC with a PD-L1 combined positive score (CPS) of ≥10, while for CPS<10, CT remains the standard. Randomized data on the most effective CT backbone (carboplatin-based vs taxane) for PD-L1-blockade are lacking. This is especially important in the context of homologous recombination deficiency (HRD) linked to the benefit of alkylating and platinum agents that may influence efficacy of PD-L1 blockade.

Methods

In this multicenter, open-label phase IIb clinical trial with a 2x2 factorial design mTNBC pts were randomized 1:1 to first-line CC±add-on or P±add-on regardless of PD-L1 expression. The add-on initially consisted of bevacizumab but changed to atezo from January 2018 onwards. Pts randomized to CC or P in first line could cross-over to P+atezo or CC+atezo in second line. Pts were included regardless of PD-L1 status and stratified according to prior (neo-)adjuvant systemic treatment (yes vs no), prior taxanes (yes vs no). The primary endpoint was progression-free survival (PFS) per RECIST v1.1, to test whether a significant interaction existed between tumor HRD status and chemotherapy backbone. Secondary endpoints included atezo benefit in relation to CC or P.

Results

N=305 pts were randomized of which n=247 to atezo vs no atezo. Median follow-up was 36.3 months(m). P+atezo significantly improved median PFS (6.5m) compared to CC+atezo (5.4m), CC (5.3m) and P (4.4m) (HR PFS P+atezo vs. CC+atezo: 0.64, 95% CI: 0.44-0.93, nominal p=0.018). Moreover, P+atezo resulted in a higher objective response rate (ORR) of 54%, compared to CC+atezo (ORR: 38%) CC (ORR: 31%) and P (ORR: 42%). The interaction of tumor HRD status with outcome after CC±add-on versus P±add-on and efficacy of atezo in relation to PD-L1 status will be presented at the meeting.

Conclusions

Our results suggest a significant PFS benefit of atezo with a taxane as CT backbone when compared to atezo with a carboplatin-based backbone in first-line treatment of mTNBC.

Clinical trial identification

NCT01898117.

Editorial acknowledgement

Legal entity responsible for the study

Dutch Breast Cancer Research Group (BOOG).

Funding

Roche.

Disclosure

M. Kok: Financial Interests, Institutional, Advisory Board, Adboard, invited speaker: Roche, BMS; Financial Interests, Institutional, Advisory Board: Daiichi, MSd, Alderaan; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Research Grant: BMS, Roche, AZ; Financial Interests, Steering Committee Member: BMS; Non-Financial Interests, Other, non-financial support research projects (ctDNA analyses for free): Natera. M. Chelushkin: Financial Interests, Personal, Stocks or ownership: BostonGene. H.M. Oosterkamp: Financial Interests, Personal, Advisory Board, Implementation Phesgo in the Netherlands (09-03-2022): Roche; Financial Interests, Personal, Advisory Board, Implementation trastuzumab-deruxtecan as second line or higher treatment in metastatic HER2+ breast cancer (17-03-2022): AstraZeneca; Financial Interests, Personal, Advisory Board, Implementation of abemaciclib in early breast cancer (06-04-2022): Ely Lilly; Financial Interests, Personal, Advisory Board, pembrolizumab eTNBC dd 09-05-2022: MSD; Financial Interests, Personal, Advisory Board, sacituzumab-govitecan in metastatic breast cancer (20-12-2022): Gilead; Financial Interests, Personal, Advisory Board, trastuzumab-deruxtecan in metastatic HER2+ breast cancer (10-01-2023): Daiichi Sankyo; Financial Interests, Personal, Advisory Board, T-DXd in HER2 low metastatic breast cancer ( 30-03-2023): AstraZeneca; Financial Interests, Personal, Advisory Board, CDK4/6 inhibitors in metastatic breast cancer (19-04-2023): Novartis; Financial Interests, Personal, Advisory Board, CDK4/6 inhibitors in early breast cancer (06-07-2023): Novartis; Financial Interests, Personal, Advisory Board, CDK4/6i after the SONIA trial (12-09-2023): Pfizer; Financial Interests, Personal, Advisory Board, capivasertib in metastatic breast cancer (09-11-2023): AstraZeneca; Financial Interests, Institutional, Research Grant, Unrestricted research grant from Roche to the NKI in order to perform the Triple B study (co-PI): Roche; Financial Interests, Institutional, Research Grant, Unrestricted research grant fro Sanofi to the NKI in order to perform the MATADOR trial (co- PI): Sanofi. S. Linn: Financial Interests, Institutional, Sponsor/Funding: Roche; Non-Financial Interests, Institutional, Advisory Role: Daiichi Sankyo, AstraZeneca, Cergentis, IBM; Financial Interests, Institutional, Research Funding: Genetech/Roche, Tesaro/GSK, Merck, AstraZeneca, Immunomedics (Gilead), Eurocept Pharmaceuticals, Agendia, Novartis; Other, Institutional, Other, Travel, accommodation expenses: Daiichi Sankyo Europe GmbH. All other authors have declared no conflicts of interest.