2785 - Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase 3 study ARIEL3 of rucaparib maintenance treatment

Background

In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo and was associated with reductions in tumour burden in pts with measurable disease (Coleman et al. Lancet. 2017;390:1949-61). This exploratory analysis evaluated the efficacy of rucaparib in ARIEL3 pts based on their best response to last platinum-based chemotherapy prior to enrolment.

Methods

Pts were randomised 2:1 to oral rucaparib (600 mg BID) or placebo. Subgroup analysis was based on a randomisation stratification factor of best response to last platinum-based chemotherapy: complete response (CR) or partial response (PR). PFS was assessed in 3 predefined nested cohorts: BRCA mutant, BRCA mutant + BRCA wild type/high loss of heterozygosity (LOH), and the intent-to-treat (ITT) population. Response was also assessed for pts with nonmeasurable disease (eg, lesions <10 mm) at baseline. For PFS and response, tumours were assessed per RECIST v1.1.

Results

The visit cutoff dates for efficacy and safety were 15 Apr 2017 and 31 Dec 2017. Rucaparib significantly improved PFS vs placebo in the CR and PR subgroups, with a similar treatment effect in both subgroups across all cohorts (Table). Of pts with nonmeasurable disease at baseline, 23/104 (22.1%) rucaparib pts and 2/56 (3.6%) placebo pts had a CR, including 7 rucaparib pts without a BRCA mutation or high LOH. The most common grade ≥3 treatment-emergent adverse event (rucaparib vs placebo) was anaemia/decreased haemoglobin (CR subgroup, 24.0% vs 0%; PR subgroup, 20.2% vs 0.8%).Table: 1001P

HRs estimated with a Cox proportional hazards model. P values were nonsignificant for the treatment by best response subgroup (CR vs PR) interaction tests for investigator-assessed PFS (BRCA-mutant cohort, P = 0.5680; BRCA-mutant + BRCA wild-type/high LOH cohort, P = 0.4092; ITT population, P = 0.7001) and BICR-assessed PFS (BRCA-mutant cohort, P = 0.9192; BRCA-mutant + BRCA wild-type/high LOH cohort, P = 0.8383; ITT population, P = 0.7976). ^aStratified log-rank P value. BICR, blinded independent central review; CI, confidence interval; HR, hazard ratio; NR, not reached.

Conclusions

Regardless of response to last platinum-based chemotherapy, rucaparib maintenance treatment significantly improved PFS vs placebo across all cohorts. Similar to pts with measurable disease at baseline, CRs were observed in rucaparib-treated pts with nonmeasurable disease. Safety was consistent across the CR and PR subgroups.

Clinical trial identification

NCT01968213.

Editorial acknowledgement

Nathan Yardley, PhD, and Shannon Davis of Ashfield Healthcare Communications (Middletown, CT, USA), funded by Clovis Oncology, Inc. (Boulder, CO, USA).

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Disclosure

J.A. Ledermann: Honoraria (self), Advisory / Consultancy: Clovis Oncology, Inc.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Pfizer; Advisory / Consultancy: Artios Pharma; Advisory / Consultancy: Cristal Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Merck/Merck Sharp & Dohme; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Roche; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Tesaro. A.M. Oza: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: Amgen; Advisory / Consultancy: Immunovaccine; Advisory / Consultancy: Verastem; Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): WebRx. D. Lorusso: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy: Tesaro. C. Aghajanian: Honoraria (self), Advisory / Consultancy, Non-remunerated activity/ies: Clovis Oncology, Inc.; Honoraria (self), Non-remunerated activity/ies: Mateon Therapeutics; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Cerulean Pharma; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: VentiRx. A. Oaknin: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy: Genmab/Seattle Genetics; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro. A. Dean: Advisory / Consultancy: Precision Oncology Australia; Advisory / Consultancy: Shire Pharmaceuticals; Advisory / Consultancy: Specialised Therapeutics Australia. N. Colombo: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: Advaxis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BIOCAD; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro. J.I. Weberpals: Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. A.R. Clamp: Travel / Accommodation / Expenses: Clovis Oncology, Inc.; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Roche. G. Scambia: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro. A. Leary: Advisory / Consultancy: Clovis Oncology, Inc.; Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): GamaMabs; Research grant / Funding (institution): Merus. R.W. Holloway: Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis Oncology, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Tesaro. M. Amenedo Gancedo: Speaker Bureau / Expert testimony: Clovis Oncology, Inc.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: PharmaMar; Speaker Bureau / Expert testimony: Roche. P.C. Fong: Advisory / Consultancy: Clovis Oncology, Inc.; Honoraria (self), Advisory / Consultancy: AstraZeneca. J.C. Goh: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Janssen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Merck Sharp & Dohme; Travel / Accommodation / Expenses: Astellas Pharma, Inc. D.M. O’Malley: Advisory / Consultancy, Research grant / Funding (institution), Non-remunerated activity/ies: Clovis Oncology, Inc.; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Gynecologic Oncology Group; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy: Myriad; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Non-remunerated activity/ies: Amgen; Research grant / Funding (institution), Non-remunerated activity/ies: ImmunoGen; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Ambry; Advisory / Consultancy: Health Analytics; Research grant / Funding (institution): Agenus; Research grant / Funding (institution): Ajinomoto; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): ERGOMED Clinical Research; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): INC Research. T. Cameron: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. L. Maloney: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. S. Goble: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. R.L. Coleman: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology, Inc.; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Esperance; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Millennium; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): GamaMabs; Research grant / Funding (institution): Genmab; Research grant / Funding (institution): Gradalis.