Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

Michael Friedlander, Ursula Matulonis, Charlie Gourley, Andreas du Bois, Ignace Vergote, Gordon Rustin, Clare Scott, Werner Meier, Ronnie Shapira-Frommer, Tamar Safra, Daniela Matei, Vadim Shirinkin, Frédéric Selle, Anitra Fielding, Elizabeth S. Lowe, Emma L. McMurtry, Stuart Spencer, Philip Rowe, Helen Mann, David ParryJonathan Ledermann

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. Methods: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). Results: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. Conclusions: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

Original languageEnglish (US)
Pages (from-to)1075-1085
Number of pages11
JournalBritish Journal of Cancer
Volume119
Issue number9
DOIs
StatePublished - Oct 30 2018
Externally publishedYes

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Platinum
Ovarian Neoplasms
Capsules
Maintenance
Drug Therapy
Placebos
Survival
Mutation
Disease-Free Survival
olaparib
Confidence Intervals
Safety
Incidence
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. / Friedlander, Michael; Matulonis, Ursula; Gourley, Charlie; du Bois, Andreas; Vergote, Ignace; Rustin, Gordon; Scott, Clare; Meier, Werner; Shapira-Frommer, Ronnie; Safra, Tamar; Matei, Daniela; Shirinkin, Vadim; Selle, Frédéric; Fielding, Anitra; Lowe, Elizabeth S.; McMurtry, Emma L.; Spencer, Stuart; Rowe, Philip; Mann, Helen; Parry, David; Ledermann, Jonathan.

In: British Journal of Cancer, Vol. 119, No. 9, 30.10.2018, p. 1075-1085.

Research output: Contribution to journalArticle

Friedlander, M, Matulonis, U, Gourley, C, du Bois, A, Vergote, I, Rustin, G, Scott, C, Meier, W, Shapira-Frommer, R, Safra, T, Matei, D, Shirinkin, V, Selle, F, Fielding, A, Lowe, ES, McMurtry, EL, Spencer, S, Rowe, P, Mann, H, Parry, D & Ledermann, J 2018, 'Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy', British Journal of Cancer, vol. 119, no. 9, pp. 1075-1085. https://doi.org/10.1038/s41416-018-0271-y
Friedlander, Michael ; Matulonis, Ursula ; Gourley, Charlie ; du Bois, Andreas ; Vergote, Ignace ; Rustin, Gordon ; Scott, Clare ; Meier, Werner ; Shapira-Frommer, Ronnie ; Safra, Tamar ; Matei, Daniela ; Shirinkin, Vadim ; Selle, Frédéric ; Fielding, Anitra ; Lowe, Elizabeth S. ; McMurtry, Emma L. ; Spencer, Stuart ; Rowe, Philip ; Mann, Helen ; Parry, David ; Ledermann, Jonathan. / Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. In: British Journal of Cancer. 2018 ; Vol. 119, No. 9. pp. 1075-1085.
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abstract = "Background: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. Methods: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79{\%} maturity) data, from the last data cut-off (9 May 2016). Results: Thirty-two patients (24{\%}) received maintenance olaparib for over 2 years; 15 (11{\%}) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6{\%}). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95{\%} confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. Conclusions: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.",
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T1 - Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

AU - Friedlander, Michael

AU - Matulonis, Ursula

AU - Gourley, Charlie

AU - du Bois, Andreas

AU - Vergote, Ignace

AU - Rustin, Gordon

AU - Scott, Clare

AU - Meier, Werner

AU - Shapira-Frommer, Ronnie

AU - Safra, Tamar

AU - Matei, Daniela

AU - Shirinkin, Vadim

AU - Selle, Frédéric

AU - Fielding, Anitra

AU - Lowe, Elizabeth S.

AU - McMurtry, Emma L.

AU - Spencer, Stuart

AU - Rowe, Philip

AU - Mann, Helen

AU - Parry, David

AU - Ledermann, Jonathan

PY - 2018/10/30

Y1 - 2018/10/30

N2 - Background: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. Methods: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). Results: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. Conclusions: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

AB - Background: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. Methods: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). Results: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55‒0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. Conclusions: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented long-term benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

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