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.
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).
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.
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.
NCT01482715, NCT01891344, NCT01968213.
Nathan Yardley, PhD, and Shannon Davis of Ashfield Healthcare Communications (Middletown, CT, USA), funded by Clovis Oncology, Inc. (Boulder, CO, USA).
Clovis Oncology, Inc.
Clovis Oncology, Inc.
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.