Abstract 2785
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
Cohort | Rucaparib, n | Placebo, n | Investigator-assessed PFS (primary endpoint) | BICR-assessed PFS (secondary endpoint) | ||
---|---|---|---|---|---|---|
Median PFS, mo; rucaparib vs placebo; P valuea | HR (95% CI) | Median PFS, mo; rucaparib vs placebo; P valuea | HR (95% CI) | |||
CR to last platinum-based chemotherapy | ||||||
BRCA mutant | 43 | 22 | 22.9 vs 7.4; P < 0.0001 | 0.30 (0.15–0.58) | NR vs 7.4; P < 0.0001 | 0.21 (0.09–0.49) |
BRCA mutant or BRCA wild type/high LOH | 82 | 41 | 13.9 vs 7.3; P < 0.0001 | 0.37 (0.23–0.60) | 24.7 vs 7.4; P < 0.0001 | 0.36 (0.21–0.64) |
ITT | 126 | 64 | 11.1 vs 5.6; P < 0.0001 | 0.33 (0.23–0.49) | 19.2 vs 5.5; P < 0.0001 | 0.34 (0.22–0.51) |
PR to last platinum-based chemotherapy | ||||||
BRCA mutant | 87 | 44 | 15.7 vs 4.9; P < 0.0001 | 0.20 (0.13–0.33) | 26.8 vs 4.9; P < 0.0001 | 0.20 (0.11–0.35) |
BRCA mutant or BRCA wild type/high LOH | 154 | 77 | 13.1 vs 4.9; P < 0.0001 | 0.29 (0.21–0.41) | 19.5 vs 4.7; P < 0.0001 | 0.32 (0.21–0.48) |
ITT | 249 | 125 | 9.0 vs 5.3; P < 0.0001 | 0.38 (0.30–0.49) | 13.6 vs 5.3; P < 0.0001 | 0.36 (0.27–0.49) |
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.
Resources from the same session
3006 - Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study.
Presenter: Violaine Randrian
Session: Poster Display session 2
Resources:
Abstract
3697 - The expression of Versican and its role in pancreatic neuroendocrine tumor
Presenter: Zhao Sun
Session: Poster Display session 2
Resources:
Abstract
6073 - Characteristics of patients with thyroid carcinoma in the united states
Presenter: Dina El-Habashy
Session: Poster Display session 2
Resources:
Abstract
2124 - The discrimination of pituitary adenomas and craniopharyngioma on MRI: from image features to texture features
Presenter: Hanyue Xu
Session: Poster Display session 2
Resources:
Abstract
3786 - Proportion of Peripheral Lymphocyte Subsets Correlates with the Progression-free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumor Patients
Presenter: Yitao Gong
Session: Poster Display session 2
Resources:
Abstract
2263 - Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Presenter: Enas Elkhouly
Session: Poster Display session 2
Resources:
Abstract
4386 - SILVELUL Project: Immunohistochemical panel analyses as potential predictive and prognostic factors in Pancreatic Neuroendocrine Tumors (PanNET) Treated with CAPTEM or Everolimus
Presenter: Ana De Jesus-Acosta
Session: Poster Display session 2
Resources:
Abstract
2302 - Carcinoid heart disease (CHD): the CRUSOE-NETs, a prospective cohort study from the French Group of Endocrine Tumors (GTE)
Presenter: Kathleen Dekeister Geoffroy
Session: Poster Display session 2
Resources:
Abstract
5749 - Safety of high doses of somatostatin analogs in well differentiated NENs in elderly
Presenter: Massimiliano Cani
Session: Poster Display session 2
Resources:
Abstract
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract