Response to pegylated liposomal doxorubicin (PLD) and weekly paclitaxel (wpac) in platinum resistant (PR) ovarian cancer (OC) by BRCA mutation status

Abstract Background Women with OC due to an underlying BRCA mutation (BRCAm) are known to have enhanced responses to platinum and PLD, but their relative response rates to wpac are unclear. Both PLD and wpac are commonly used in women with PROC. Our aim was to assess the response rates to both agents, stratified by BRCAm staus. Methods Women with PR OC treated at The Royal Marsden Hospital between 2007 and 2017 with known BRCAm status were identified from the electronic patient record. Included patients underwent a minimum of 3 cycles and radiological restaging for inclusion. The primary endpoint was radiological response (RR) by BRCA status - BRCAm or BRCA wildtype (WT). Secondary endpoints were clinical benefit rate (CBR), CA-125 response, and line of treatment as a predictor of response. Results 231 pt were identified, 38 BRCAm, 193 WT; median age 58 yrs (36-88) BRCAm, 62 yrs (44-85) WT. Histology was 90% HGS, 4% endometroid, 3% clear cell, 1% mucinous, 2% other. Overall 102 (44%) were treated with PLD; 129 (56%) received wpac with RR 14% PLD and 38% wpac; CBR of 49% PLD and 83% wpac (p = 0.01). When stratified by BRCAm, RR to PLD was 28% (BRCAm) vs 13% (WT; p = 0.01); and wpac 37% (BRCAm) vs 38% (WT, ns). CBR was 64% (BRCAm) vs 48% (WT) with PLD (p = 0.02) and 81% vs 83% with wpac (WT, ns). GCIG CA-125 responses were present in 110/231 (48%) – 24 PLD and 86 wpac, for CA-125 RR of 24% and 66% respectively (p  Conclusions Within the limits of a retrospective audit, BRCAm carriers had significantly higher RR to PLD than WT patients; with equivalent responses to wpac. Wpac may be a preferred choice over PLD in BRCA WT patients with PROC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.