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Poster Display session 2

3496 - Integrated safety analysis of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with ovarian cancer in the treatment and maintenance settings

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Ovarian Cancer

Presenters

Rebecca Kristeleit

Citation

Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250

Authors

R. Kristeleit1, A.M. Oza2, A. Oaknin3, C. Aghajanian4, A.V. Tinker5, O. Tredan6, D.M. O'Malley7, A. Leary8, G.E. Konecny9, D. Lorusso10, J.I. Weberpals11, S. Goble12, L. Maloney13, T. Cameron14, E. Swisher15, I.A. McNeish16, R. Shapira-Frommer17, J.A. Ledermann18, R.L. Coleman19

Author affiliations

  • 1 Department Of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, WC1E - London/GB
  • 2 Division Of Medical Oncology And Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto/CA
  • 3 Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), 08035 - Barcelona/ES
  • 4 Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 5 Medical Oncology, BC Cancer Agency, Vancouver/CA
  • 6 Department Of Medical Oncology, Centre Léon Bérard and University Claude Bernard and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Lyon/FR
  • 7 Clinical Research Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus/US
  • 8 Gynecologic Unit, Gustave Roussy Cancer Center, INSERM U981, and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Villejuif/FR
  • 9 Department Of Medicine, University of California Los Angeles, Santa Monica/US
  • 10 Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 20133 - Rome/IT
  • 11 Division Of Gynecologic Oncology, Ottawa Hospital Research Institute, Ottawa/CA
  • 12 Biostatistics, Clovis Oncology, Inc., Boulder/US
  • 13 Clinical Development, Clovis Oncology, Inc., Boulder/US
  • 14 Clinical Science, Clovis Oncology UK Ltd., Cambridge/GB
  • 15 Division Of Gynecologic Oncology, University of Washington, Seattle/US
  • 16 Department Of Surgery And Cancer, Imperial College London, London/GB
  • 17 Department Of Oncology, Chaim Sheba Medical Center, Tel HaShomer/IL
  • 18 Department Of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, London/GB
  • 19 Department Of Gynecologic Oncology And Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston/US

Resources

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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

TEAEAny gradeGrade ≥3
n (%)Time to onset, Median (95% CI), daysn (%)Time to onset, Median (95% CI), days
Any TEAE937 (100)-579 (61.8)-
Nausea721 (76.9)5 (4–5)43 (4.6)35 (13–71)
Asthenia/fatiguea685 (73.1)15 (13–15)90 (9.6)53 (37–68)
Vomiting397 (42.4)15 (13–23)40 (4.3)42 (14–85)
Anaemia/haemoglobin decreaseda395 (42.2)56 (53–57)217 (23.2)83 (74–85)
Abdominal paina388 (41.4)45 (33–56)40 (4.3)112 (46–189)
Constipation356 (38.0)29 (22–43)15 (1.6)120 (81–232)
ALT/AST increaseda352 (37.6)15 (14–15)99 (10.6)15 (15–16)
Dysgeusia352 (37.6)7 (5–9)1 (0.1)197 (NA)
Decreased appetite307 (32.8)22 (16–29)19 (2.0)85 (25–127)
Diarrhoea305 (32.6)29 (17–35)15 (1.6)31 (11–103)
Thrombocytopenia/ platelets decreaseda245 (26.1)52 (43–57)56 (6.0)47 (29–63)
a

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.

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