Abstract 763P
Background
Ovarian Cancer (OC) patients (pts) who are not eligible for platinum rechallenge, are candidates for single-agent non-platinum treatments though chances of response are low. The predictive role of BRCA mutations (mut), which has been studied thoroughly for platinum compounds, is not well defined in this setting. We aimed to describe the single-agent activity of non-platinum compounds in a large multicentric cohort of OC pts with a known BRCA status.
Methods
We retrospectively recorded and analyzed overall response rate (ORR) and median progression free survival (mPFS) in OC pts with known BRCA status treated with pegylated liposomal doxorubicin (PLD), paclitaxel (ptx), gemcitabine (gem), topotecan, oral cyclophosphamide and etoposide as single agents in any line of therapy.
Results
432 OC pts were recorded, among them 98 (23%) were BRCAmut and 334 (77%) were BRCAwt. Median overall survival (mOS) was 102.5 months (mo) for BRCAwt and 141 mo for BRCAmut pts (p <0.005). 53 pts received PLD (48 BRCAwt and 5 BRCAmut), ORR in the whole population was 5.7% (3/53), with 1/48 responding pt (2.1%) in the BRCAwt group versus (vs) 2/5 (40.0%) in the BRCAmut group (p=0.021) and a mPFS of 16.1 weeks(w) vs 23.9w for BRCAwt and BRCAmut pts, respectively (p>0.05). 36 patients received ptx; ORR was 27.8%, 24.0% and 36.4% in the overall population, BRCAwt and BRCAmut subgroup respectively (p>0.05). Gem was administered to 38 pts with an ORR of 18.9%, 13.3% and 42.9% in the overall population, BRCAwt and BRCAmut pts, respectively (p>0.05). mPFS in BRCAmut pts treated with gem or ptx was numerically higher than BRCAwt ones. Results from the remaining agents do not suggest a higher activity in the BRCAmut population (Table). Table: 763P
ORR and mPFS according to treatment regimen
| Monotherapy | ORR in the whole population | ORR in BRCA wt pts | ORR in BRCAmut pts | p value (ORR) | mPFS (w) in BRCA wt pts | mPFS (w) in BRCA mut pts | p value (mPFS) |
| PLD | 3/53 (5.7%) | 1/48 (2.1%) | 2/5 (40.0%) | p=0.021 | 16.1 | 23.9 | p=0.973 |
| Paclitaxel | 10/36 (27.8%) | 6/25 (24.0%) | 4/11 (36.4%) | p=0.35 | 20.9 | 23.9 | p=0.825 |
| Gemcitabine | 7/37 (18.9%) | 4/30 (13.3%) | 3/7 (42.9%) | p=0.11 | 15.1 | 18.6 | p=0.19 |
| Topotecan | 3/30 (10.0%) | 3/24 (12.5%) | 0/6 (0%) | p=0.50 | 21.0 | 15.4 | P==0.25 |
| Etoposide | 4/27 (14.8%) | 4/22 (18.2%) | 0/5 (0%) | p=0.42 | 9.6 | 17.1 | p=0.84 |
| Cyclophosphamide | 2/34 (5.9%) | 2/30 (6.7%) | 0/4 (0%) | p=0.78 | 15.0 | 12.4 | p=0.69 |
Conclusions
Our real-life data confirm a longer survival for BRCAmut pts and a low activity of single-agents in this setting. Nevertheless, considering ORR and PFS, none of these drugs showed a clear lack of activity in BRCAmut or BRCAwt cohorts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
U. De Giorgi: Financial Interests, Personal, Advisory Board: Janssen-Cilag; Non-Financial Interests, Other, travel support: Janssen-Cilag; Financial Interests, Personal, Other, Lectures and advisory board: Astellas; Financial Interests, Research Grant: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other, Lectures: Pfizer; Non-Financial Interests, Other, travel support: Pfizer; Financial Interests, Personal, Other, Lectures and advisory board: BMS; Non-Financial Interests, Other, travel support: BMS; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Lectures and advisory board: Ipsen; Non-Financial Interests, Other, travel support: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Other, travel support: Roche; Financial Interests, Research Grant: Roche; Financial Interests, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pharmamar. M. Di Maio: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Research Grant: Tesaro - GlaxoSmithKline. All other authors have declared no conflicts of interest.