813MO - Efficacy of subsequent chemotherapy for patients with BRCA1/2 mutated platinum-sensitive recurrent epithelial ovarian cancer (EOC) progressing on olaparib vs placebo: The SOLO2/ENGOT Ov-21 trial

Background

SOLO2 (ENGOT Ov-21; NCT01874353) demonstrated that maintenance olaparib (O) in patients (pts) with platinum-sensitive relapsed EOC and a BRCA1/2 mutation led to clinically significant survival benefit. We report on the efficacy of subsequent chemotherapy at the time of disease progression.

Methods

First subsequent treatment was analysed in pts who progressed according to RECIST1.1 in the O and placebo (P) arms. We conducted a post-hoc analysis of time to second progression (TTSP) calculated from the date of RECIST progression after O maintenance to next progression or death as a surrogate of first post-olaparib treatment progression-free survival.

Results

106/195 (54%) and 80/99 (81%) pts had a RECIST progression in the O and P arms respectively. Pt baseline demographics were balanced between both arms. Overall, 161/186 (87%) pts received a first subsequent therapy, including a chemotherapy in 150/161 (93%) and a PARP inhibitor in 29/161 (18%, all in the P arm). In the P arm, 33/75 (44%) and 42/75 (56%) pts received a non-platinum and a platinum-based chemotherapy respectively vs 32/86 (37%) and 54/86 (63%) in the O arm. Overall, in pts receiving subsequent treatment, TTSP was longer in the placebo compared to the O arm: 11.1 vs 7 months (HR 1.93; 95% CI [1.35-2.76]). TTSP was 14.3 vs 7m with platinum-based chemotherapy and 8.3 vs 5.5m with non-platinum chemotherapy in the P and O arm respectively.

Conclusions

In this SOLO2 post-hoc comparison, some degree of resistance to standard subsequent platinum and non-platinum chemotherapy is noted in the O arm. However, the TTSP reduction being not at the expense of overall survival, it suggests that the earlier use of O remains optimal in this population. The best post O management should be studied in prospective manner.

Clinical trial identification

NCT01874353.

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

J-S. Frenel: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BioCad; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis pharma SAS; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer Pharmaceuticals Israel; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Tesaro. D. Berton-Rigaud: Advisory/Consultancy, Board: AstraZeneca; Advisory/Consultancy, Board: Tesaro; Travel/Accommodation/Expenses, ESMO ASCO: Pfizer; Travel/Accommodation/Expenses, ESMO ASCO: PharmaMar. L. Vidal: Full/Part-time employment: Syneos Health ( CRO). P. Pautier: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: GSK. J.A. Ledermann: Honoraria (self), Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Artios; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy: Cristal Therapeutics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Tesaro; Speaker Bureau/Expert testimony: Tesaro/GSK; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MSD Oncology. R.T. Penson: Honoraria (self), Advisory/Consultancy, Other Relationship: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai Inc; Honoraria (self): Genentech/Roche; Honoraria (self), Advisory/Consultancy: Janssen Oncology (J & J); Honoraria (self), Advisory/Consultancy: Mersana Therapeutics, Inc.; Honoraria (self): Newlink Genetics; Honoraria (self), Advisory/Consultancy: Sutro Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Vascular Biogenics Ltd; Advisory/Consultancy: Amgen; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Care4ward; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy: Merck; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Cerulean Pharma; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Sanofi; Licensing/Royalties: Blackwell Publishing; Licensing/Royalties: BMJ; Licensing/Royalties: UpToDate. A.M. Oza: Honoraria (self): Intas; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Merck KGaA; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Immunovaccine; Non-remunerated activity/ies, Other Relationship: Clovis Oncology; Non-remunerated activity/ies, Other Relationship: Tesaro. J. Korach: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD Oncology. S. Pignata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): GSK; Honoraria (self): Clovis; Honoraria (self): PharmaMar; Honoraria (self): Incyte. N. Colombo: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Tesaro; Advisory/Consultancy: BioCad; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: GSK; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda. T-W. Park-Simon: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: Daichi; Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: MS. K. Tamura: Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): MSD; Research grant/Funding (self): Chugai; Research grant/Funding (self): AstraZeneca. G.S. Sonke: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Roche. A. Freimund: Licensing/Royalties, as CPI of the clinical trial, PRECISE, that is receiving study drug and part study funding: BeiGene Pharmaceuticals. C.K. Lee: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Takeda. E. Pujade-Lauraine: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer/EMD; Advisory/Consultancy: Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.