Abstract 225P
Background
Patients (pts) with germinal BRCA mutated (gBRCAm) breast cancer (BC) have an enhanced sensitivity to platinum-based chemotherapy (PBC) and PARP-inhibitors (PARPi). As reported in ovarian cancer, sensitivity and resistance to these treatments partially overlap. In gBRCAm BC, it is unclear if prior exposure to PARPi/PBC affects tumor response to subsequent PBC/PARPi.
Methods
We conducted a retrospective, multicentre observational study to assess the benefit of PARPi post-PBC and viceversa in pts with gBRCAm BC. Pts included received: (neo)adjuvant PBC and then PARPi in advanced setting (group [Gr] 1); PBC followed by PARPi (Gr2), or PARPi followed by PBC (Gr3) in advanced setting. We reported median progression free survival (mPFS) and disease control rate (DCR) for each group. Correlative analyses were provided (significance at p<0.05).
Results
59 pts from 5 centers were included. Pts characteristics and outcomes are reported in the table. PARPi-mPFS in metastatic setting of pts from Gr1 (N=9) was 4.8 months (mo). DCR was of 67%. In Gr2 (N=31), mPFS with PBC and subsequent PARPi were 4.3 and 4.5 mo; DCRs were of 97% and 45%. Age<46 and platinum free interval (PFI)>6mo were associated with longer PARPi-PFS (p=.009 and .016). PBC-PFS>6mo and PFI>6mo were associated with longer PARPi-DCR (p=.031 and .032). Pts in Gr3 (N=21) reported a mPFS of 5.0 with PARPi and 1.8 mo with subsequent PBC, DCRs were of 67 and 14%. PARPi in earlier lines (1-2) was associated with longer PBC-PFS (p=.020). PARPi-PFS>9mo and PARPi-FI>6mo were associated with longer PBC-DCR (p=.015 and .026).
Table: 225P
Pts characteristics and outcomes
| Gr1 (N=9) | Gr2 (N=31) | Gr3 (N=21) | ||||
| Age at diagnosis – median (range) | 38 (29-62) | 40 (28-72) | 39 (28-62) | |||
| Visceral disease – % | 67% | 81% | 86% | |||
| De novo disease – % | 0% | 13% | 24% | |||
| BRCA1/BRCA2/NA – % | 56/44/0% | 48/39/13% | 29/62/10% | |||
| TNBC/Luminal-like – % | 67/33% | 52/48% | 33/67% | |||
| PARP line (1-2/>2) – % | 67/33% | 29/71% | 5/95% | |||
| NA-PBC | PARPi post-NA-PBC | PBC | PARPi post-PBC | PARPi | PBC post-PARPi | |
| N. of line – median (range) | NA | 2 (2-5) | 2 (1-10) | 3 (2-12) | 3 (1-11) | 4 (2-13) |
| PFS – median (range) | NA | 4.8 (0.9-25.4) | 4.3 (1.5-23.8) | 4.5 (0.3-35.7) | 5.0 (0.9-12.4) | 1.8 (0.1-5.0) |
| DCR – % | NA | 67% | 97% | 45% | 67% | 14% |
NA: not applicable; (NA)-PBC: (neoadjuvant) platinum-based chemotherapy; TNBC: triple negative BC
Conclusions
Sensitivity and resistance to PARPi and PBC partially overlap in BC. mPFS on PBC/PARPi and PFI/PARPi-FI represent two potential predictive factors of DCR for the subsequent treatment with PARPi/PBC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Berardi: Financial Interests, Personal, Advisory Board: AstraZeneca, Boeringher Ingelheim, Novartis, MSD, Otsuka, Lilly, Roche, Amgen, GSK, EISAI; Financial Interests, Institutional, Funding: Roche, AstraZeneca. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Sanofi, merck serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, Glaxo Smith kline, Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. G. Curigliano: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Lilly, Pfizer, Veracyte, BMS, Merck, Exact Sciences, Celcuity; Financial Interests, Personal, Other, Advisory Board: Ellipsis; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Merck; Financial Interests, Institutional, Funding, Phase I studies: BMS, Novartis, AstraZeneca, Daiichi Sankyo, Roche, Blueprint Medicine, Kymab, Astellas, Sanofi, Philogen; Financial Interests, Institutional, Invited Speaker, Phase I clinical basket trial: Relay Therapeutics; Non-Financial Interests, Invited Speaker, No compensation for this role. This a public national company for cancer prevention: Lega Italiana Lotta ai Tumori; Non-Financial Interests, Officer, Italian National Health Council as Advisor for Ministry of Health: Consiglio Superiore di Sanità; Non-Financial Interests, Advisory Role, Member of the Scientific Council. Patient advocacy association: Europa Donna; Non-Financial Interests, Advisory Role, Cancer Research Foundation: Fondazione Beretta; Non-Financial Interests, Officer, Member of the Advisory Council: EUSOMA; Non-Financial Interests, Officer, ESMO Clinical Practice Guidelines Chair: ESMO. All other authors have declared no conflicts of interest.