Abstract 3496
Background
Rucaparib is approved in the European Union and the United States for use as treatment or maintenance for women with ovarian cancer. Here we present an integrated analysis of rucaparib safety in these settings.
Methods
Treatment-emergent adverse events (TEAEs) of any grade, grade ≥3 TEAEs, median time to onset of TEAEs, and discontinuations due to a treatment-related TEAE were evaluated for all pts with epithelial ovarian, fallopian tube, or primary peritoneal cancer who received ≥1 dose of rucaparib 600 mg in CO-338-010 (Study 10; NCT01482715), ARIEL2 (CO-338-017; NCT01891344), or ARIEL3 (CO-338-014; NCT01968213).
Results
The integrated safety analysis included 937 rucaparib-treated pts from the treatment (Study 10, n = 74; ARIEL2, n = 491) and maintenance (ARIEL3, n = 372) settings (visit cutoff date, 31 December 2017). Any-grade TEAEs occurring in ≥ 20% of pts are shown in the table, along with median time to onset. Overall, 99/937 (10.6%) pts discontinued due to an any-grade treatment-related TEAE (treatment setting: 53/565 [9.4%]); maintenance setting: 46/372 [12.4%]), the most frequent of which were asthenia/fatigue (21/937 [2.2%]), anaemia/haemoglobin decreased (18/937 [1.9%]), and thrombocytopenia/platelets decreased (17/937 [1.8%]). The most frequent grade ≥3 treatment-related TEAE leading to discontinuation was anaemia/haemoglobin decreased (15/937 [1.6%]); only 2/937 (0.2%) pts discontinued due to grade ≥3 AST/ALT increased. Any-grade treatment-emergent myelodysplastic syndrome and/or acute myeloid leukaemia were reported in 5/937 (0.5%) pts.
Conclusions
This integrated analysis aligns with the known safety profile of rucaparib. Any-grade gastrointestinal TEAEs and asthenia/fatigue typically occurred within the first month, with any-grade haematological TEAEs occurring later. Onset of grade ≥3 TEAEs mainly occurred after month 1.Table: 1002P
TEAE | Any grade | Grade ≥3 | ||
---|---|---|---|---|
n (%) | Time to onset, Median (95% CI), days | n (%) | Time to onset, Median (95% CI), days | |
Any TEAE | 937 (100) | - | 579 (61.8) | - |
Nausea | 721 (76.9) | 5 (4–5) | 43 (4.6) | 35 (13–71) |
Asthenia/fatiguea | 685 (73.1) | 15 (13–15) | 90 (9.6) | 53 (37–68) |
Vomiting | 397 (42.4) | 15 (13–23) | 40 (4.3) | 42 (14–85) |
Anaemia/haemoglobin decreaseda | 395 (42.2) | 56 (53–57) | 217 (23.2) | 83 (74–85) |
Abdominal paina | 388 (41.4) | 45 (33–56) | 40 (4.3) | 112 (46–189) |
Constipation | 356 (38.0) | 29 (22–43) | 15 (1.6) | 120 (81–232) |
ALT/AST increaseda | 352 (37.6) | 15 (14–15) | 99 (10.6) | 15 (15–16) |
Dysgeusia | 352 (37.6) | 7 (5–9) | 1 (0.1) | 197 (NA) |
Decreased appetite | 307 (32.8) | 22 (16–29) | 19 (2.0) | 85 (25–127) |
Diarrhoea | 305 (32.6) | 29 (17–35) | 15 (1.6) | 31 (11–103) |
Thrombocytopenia/ platelets decreaseda | 245 (26.1) | 52 (43–57) | 56 (6.0) | 47 (29–63) |
Combined terms. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CI, confidence interval; NA, not applicable due to only 1 case of dysguesia.
Clinical trial identification
NCT01482715, NCT01891344, 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
R.S. Kristeleit: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: Roche; 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. 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: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: 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: Tesaro; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Cerulean Pharma; Honoraria (self), Advisory / Consultancy: VentiRx. A.V. Tinker: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. 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): Tesaro; Advisory / Consultancy, Research grant / Funding (institution): Gynecologic Oncology Group; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy: Myriad; 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. A. Leary: Advisory / Consultancy: Clovis Oncology, Inc.; Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Pfizer, Inc.; Advisory / Consultancy: PharmaMar; Research grant / Funding (institution): GamaMabs; Research grant / Funding (institution): Merus. G.E. Konecny: Speaker Bureau / Expert testimony: Clovis Oncology, Inc.; Speaker Bureau / Expert testimony: AstraZeneca; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Merck; Honoraria (self): Novartis. D. Lorusso: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy: ImmunoGen; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: Takeda. J.I. Weberpals: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): AbbVie. S. Goble: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. L. Maloney: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. T. Cameron: Shareholder / Stockholder / Stock options, Employee: Clovis Oncology, Inc. I.A. McNeish: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Takeda. R. Shapira-Frommer: Advisory / Consultancy: Clovis Oncology, Inc.; Advisory / Consultancy: Merck/Merck Sharp & Dohme. 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: Roche; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Tesaro. R.L. Coleman: Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology, Inc.; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck; 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): Millennium; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Advisory / Consultancy: Bayer; Advisory / Consultancy: GamaMabs; Advisory / Consultancy: Genmab; Advisory / Consultancy: Gradalis. All other authors have declared no conflicts of interest.
Resources from the same session
1309 - Quantifying the Effects of the Korean National Cancer Screening Program on Cervical Cancer Mortality
Presenter: Nhung Bui
Session: Poster Display session 2
Resources:
Abstract
1346 - Spread of tumor and adverse events after modified radical hysterectomy for FIGO Stage IB1 cervical cancer patients with tumor diameter preoperatively estimated 2 cm or less: Japan Clinical Oncology Group trial (JCOG1101); exploratory analysis before primary analysis.
Presenter: Takahide Arimoto
Session: Poster Display session 2
Resources:
Abstract
5352 - Impact of Combined Interstitial and Intracavitary Brachytherapy in locally advanced Cervical cancer: A Survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
2049 - Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer
Presenter: Chel Hun Choi
Session: Poster Display session 2
Resources:
Abstract
1923 - Disparities starting adjuvant chemotherapy for locally advanced cervix cancer in the international, academic, randomised, phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)
Presenter: Linda Mileshkin
Session: Poster Display session 2
Resources:
Abstract
3284 - Primary results from CECILIA, a global single-arm phase 2 study evaluating bevacizumab (BEV), carboplatin (C) and paclitaxel (P) for advanced cervical cancer (aCC)
Presenter: Andres Redondo
Session: Poster Display session 2
Resources:
Abstract
843 - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: a meta-analysis
Presenter: Xiaobin Gu
Session: Poster Display session 2
Resources:
Abstract
1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit
Presenter: Mariana Scaranti
Session: Poster Display session 2
Resources:
Abstract
872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA
Presenter: Xuan Jiang
Session: Poster Display session 2
Resources:
Abstract
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract