Olaparib plus bevacizumab as first-line maintenance in ovarian cancer

I. Ray-Coquard, P. Pautier, S. Pignata, D. Pérol, A. González-Martín, R. Berger, K. Fujiwara, I. Vergote, N. Colombo, J. Mäenpää, F. Selle, J. Sehouli, D. Lorusso, E. M. Guerra Alía, A. Reinthaller, S. Nagao, C. Lefeuvre-Plesse, U. Canzler, G. Scambia, A. LortholaryF. Marmé, P. Combe, N. De Gregorio, M. Rodrigues, P. Buderath, C. Dubot, A. Burges, B. You, E. Pujade-Lauraine, P. Harter

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.

Original languageEnglish
Pages (from-to)2416-2428
Number of pages13
JournalNew England Journal of Medicine
Volume381
Issue number25
DOIs
Publication statusPublished - Dec 19 2019

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ray-Coquard, I., Pautier, P., Pignata, S., Pérol, D., González-Martín, A., Berger, R., ... Harter, P. (2019). Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. New England Journal of Medicine, 381(25), 2416-2428. https://doi.org/10.1056/NEJMoa1911361

Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. / Ray-Coquard, I.; Pautier, P.; Pignata, S.; Pérol, D.; González-Martín, A.; Berger, R.; Fujiwara, K.; Vergote, I.; Colombo, N.; Mäenpää, J.; Selle, F.; Sehouli, J.; Lorusso, D.; Guerra Alía, E. M.; Reinthaller, A.; Nagao, S.; Lefeuvre-Plesse, C.; Canzler, U.; Scambia, G.; Lortholary, A.; Marmé, F.; Combe, P.; De Gregorio, N.; Rodrigues, M.; Buderath, P.; Dubot, C.; Burges, A.; You, B.; Pujade-Lauraine, E.; Harter, P.

In: New England Journal of Medicine, Vol. 381, No. 25, 19.12.2019, p. 2416-2428.

Research output: Contribution to journalArticle

Ray-Coquard, I, Pautier, P, Pignata, S, Pérol, D, González-Martín, A, Berger, R, Fujiwara, K, Vergote, I, Colombo, N, Mäenpää, J, Selle, F, Sehouli, J, Lorusso, D, Guerra Alía, EM, Reinthaller, A, Nagao, S, Lefeuvre-Plesse, C, Canzler, U, Scambia, G, Lortholary, A, Marmé, F, Combe, P, De Gregorio, N, Rodrigues, M, Buderath, P, Dubot, C, Burges, A, You, B, Pujade-Lauraine, E & Harter, P 2019, 'Olaparib plus bevacizumab as first-line maintenance in ovarian cancer', New England Journal of Medicine, vol. 381, no. 25, pp. 2416-2428. https://doi.org/10.1056/NEJMoa1911361
Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. New England Journal of Medicine. 2019 Dec 19;381(25):2416-2428. https://doi.org/10.1056/NEJMoa1911361
Ray-Coquard, I. ; Pautier, P. ; Pignata, S. ; Pérol, D. ; González-Martín, A. ; Berger, R. ; Fujiwara, K. ; Vergote, I. ; Colombo, N. ; Mäenpää, J. ; Selle, F. ; Sehouli, J. ; Lorusso, D. ; Guerra Alía, E. M. ; Reinthaller, A. ; Nagao, S. ; Lefeuvre-Plesse, C. ; Canzler, U. ; Scambia, G. ; Lortholary, A. ; Marmé, F. ; Combe, P. ; De Gregorio, N. ; Rodrigues, M. ; Buderath, P. ; Dubot, C. ; Burges, A. ; You, B. ; Pujade-Lauraine, E. ; Harter, P. / Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. In: New England Journal of Medicine. 2019 ; Vol. 381, No. 25. pp. 2416-2428.
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abstract = "BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95{\%} confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95{\%} CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95{\%} CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.",
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T1 - Olaparib plus bevacizumab as first-line maintenance in ovarian cancer

AU - Ray-Coquard, I.

AU - Pautier, P.

AU - Pignata, S.

AU - Pérol, D.

AU - González-Martín, A.

AU - Berger, R.

AU - Fujiwara, K.

AU - Vergote, I.

AU - Colombo, N.

AU - Mäenpää, J.

AU - Selle, F.

AU - Sehouli, J.

AU - Lorusso, D.

AU - Guerra Alía, E. M.

AU - Reinthaller, A.

AU - Nagao, S.

AU - Lefeuvre-Plesse, C.

AU - Canzler, U.

AU - Scambia, G.

AU - Lortholary, A.

AU - Marmé, F.

AU - Combe, P.

AU - De Gregorio, N.

AU - Rodrigues, M.

AU - Buderath, P.

AU - Dubot, C.

AU - Burges, A.

AU - You, B.

AU - Pujade-Lauraine, E.

AU - Harter, P.

PY - 2019/12/19

Y1 - 2019/12/19

N2 - BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.

AB - BACKGROUND: Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS: We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. RESULTS: Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. CONCLUSIONS: In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.

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