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
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract