Abstract 821P
Background
Maintenance treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib significantly improved progression-free survival vs placebo regardless of biomarker status in patients with recurrent ovarian cancer in the phase III ARIEL3 study (NCT01968213). This exploratory analysis evaluated the timing of treatment-emergent adverse events (TEAEs).
Methods
Patients were randomised 2:1 to receive oral rucaparib (600 mg twice daily) or placebo until disease progression, unacceptable toxicity or other reason for discontinuation. Time to onset of TEAEs was assessed.
Results
Of the 564 patients randomised in ARIEL3, 561 patients (372 for rucaparib and 189 for placebo) were included in the safety population (updated visit cut-off date, 31 December 2017). Median duration of treatment was 8.3 months for rucaparib and 5.5 months for placebo. Overall, 15.3% of patients receiving rucaparib and 1.6% of patients receiving placebo discontinued treatment due to TEAEs (excluding disease progression). Safety data, including median time to onset of the first event, for TEAEs occurring in ≥35% of patients are presented in the table Table: 821P
| TEAE | Patients with TEAE, n (%) | Patients with dose reduction or treatment interruption due to TEAE, n (%) | Median time to first onset, days (95% CI) | |||
| Rucaparib | Placebo | Rucaparib | Placebo | Rucaparib | Placebo | |
| Nausea | 282 (75.8) | 69 (36.5) | 56 (15.1) | 2 (1.1) | 5 (4–6) | 17 (7–57) |
| Asthenia/fatiguea | 263 (70.7) | 84 (44.4) | 46 (12.4) | 6 (3.2) | 15 (15–20) | 30 (16–37) |
| Dysgeusia | 148 (39.8) | 13 (6.9) | 5 (1.3) | 0 | 10 (6–15) | 11 (3–29) |
| Anaemia/decreased haemoglobina | 145 (39.0) | 10 (5.3) | 66 (17.7) | 1 (0.5) | 67 (57–85) | 54 (15–140) |
| Constipation | 141 (37.9) | 46 (24.3) | 10 (2.7) | 1 (0.5) | 40 (29–55) | 46 (23–81) |
| Vomiting | 138 (37.1) | 29 (15.3) | 35 (9.4) | 2 (1.1) | 24 (15–39) | 84 (36–129) |
aCombined terms.TEAE, treatment-emergent adverse events.
.Conclusions
In the rucaparib group, median time to first onset for most of the frequently reported non-haematological TEAEs was within 1 month of therapy. In the rucaparib and placebo groups, median time to first onset of anaemia/decreased haemoglobin occurred within 3 and 2 months of therapy, respectively.
Clinical trial identification
NCT01968213.
Editorial acknowledgement
Medical writing support was provided by Andrew Croskery, MPharm, PhD (Clovis Oncology, Ltd., London, UK); editorial support funded by Clovis Oncology was provided by Frederique H. Evans, MBS, of Ashfield Healthcare Communications.
Legal entity responsible for the study
Clovis Oncology, Inc.
Funding
Clovis Oncology, Inc.
Disclosure
A. Dean: Advisory/Consultancy: Precision Oncology Australia; Advisory/Consultancy: Shire Pharmaceuticals; Advisory/Consultancy: Specialised Therapeutics Australia. A.M. Oza: Advisory/Consultancy, Steering committee: Clovis Oncology; Advisory/Consultancy, Steering committee: AstraZeneca; Advisory/Consultancy, Steering committee: Tesaro. D. Lorusso: Advisory/Consultancy: Clovis Oncology; 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: Advisory/Consultancy, Research grant/Funding (self): AbbVie; Advisory/Consultancy, Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): Clovis Oncology; Advisory/Consultancy: Eisai/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy: Mersana Therapeutics; Advisory/Consultancy: Roche; Advisory/Consultancy: Tesaro; Research grant/Funding (self): AstraZeneca. A. Oaknin: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Genmab/Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): ImmunoGen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): AbbVie Deutschland; Research grant/Funding (institution): Ability Pharmaceuticals; Research grant/Funding (institution): Advaxis; Research grant/Funding (institution): Aeterna Zentaris; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Aprea Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Merck/Merck Sharp & Dohme; Research grant/Funding (institution): Millennium Pharmaceuticals. N. Colombo: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Advaxis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Biocad; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Pfizer; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Tesaro. J. Weberpals: Research grant/Funding (self): AbbVie; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. A.R. Clamp: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Clovis Oncology. G. Scambia: Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Roche; Advisory/Consultancy: Tesaro. A. Leary: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy, Research grant/Funding (institution): Ability Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Biocad; Advisory/Consultancy: GamaMabs; Advisory/Consultancy: Genmab/Seattle Genetics; Advisory/Consultancy: Gritstone; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Agenus; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Iovance; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Sanofi. R.W. Holloway: Advisory/Consultancy, Speaker Bureau/Expert testimony: Clovis Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Tesaro. M. Amenedo Gancedo: Speaker Bureau/Expert testimony: Clovis Oncology; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: PharmaMar; Speaker Bureau/Expert testimony: Roche. P.C. Fong: Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: AstraZeneca. J.C. Goh: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Tesaro; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Astellas. D.M. O'Malley: Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Genelux; Advisory/Consultancy, Research grant/Funding (institution): Iovance Biotherapeutics; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Novocure; Advisory/Consultancy: Regeneron; Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Advisory/Consultancy, Research grant/Funding (institution): Agenus; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Ambry; Advisory/Consultancy, Research grant/Funding (institution): Gynecologic Oncology Group Foundation; Speaker Bureau/Expert testimony: National Comprehensive Cancer Network; Research grant/Funding (institution): Ajinomoto; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Cerulean Pharma; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): ERGOMED Clinical Research; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): INC Research; Research grant/Funding (institution): inVentiv Health Clinical; Research grant/Funding (institution): Janssen Research and Development; Research grant/Funding (institution): Ludwig Institute for Cancer Research; Research grant/Funding (institution): New Mexico Cancer Care Alliance; Research grant/Funding (institution): PRA International; Research grant/Funding (institution): Regeneron Pharmaceuticals; Research grant/Funding (institution): Serono; Research grant/Funding (institution): Stemcentrx; Research grant/Funding (institution): Tracon Pharmaceuticals; Research grant/Funding (institution): VentiRx; Research grant/Funding (institution): Yale University. T. Cameron, L. Maloney, S. Goble: Shareholder/Stockholder/Stock options, Full/Part-time employment: Clovis Oncology. R.L. Coleman: Advisory/Consultancy, Research grant/Funding (self): Clovis Oncology; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Gateway Foundation; Advisory/Consultancy, Research grant/Funding (self): Janssen; Research grant/Funding (self): Judy Reis/Albert Pisani, MD, Ovarian Cancer Research Fund; Research grant/Funding (self): Merck; Research grant/Funding (self): National Institutes of Health; Advisory/Consultancy, Research grant/Funding (self): Roche/Genentech; Research grant/Funding (self): V-Foundation; Advisory/Consultancy: Agenus; Advisory/Consultancy: GamaMabs; Advisory/Consultancy: Genmab; Advisory/Consultancy: OncoQuest; Advisory/Consultancy: Pfizer (Medivation); Advisory/Consultancy: Regeneron; Advisory/Consultancy: Tesaro; Officer/Board of Directors, Endowment: Ann Rife Cox Chair in Gynecology. J.A. Ledermann: Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: Artios Pharma; Advisory/Consultancy: Cristal Therapeutics; Advisory/Consultancy, Research grant/Funding (self): Merck/Merck Sharp & Dohme; Advisory/Consultancy: Regeneron; Advisory/Consultancy: Roche; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Tesaro.