TY - JOUR
T1 - Updated progression-free survival and final overall survival with maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial
AU - Lorusso, Domenica
AU - Mouret-Reynier, Marie-Ange
AU - Harter, Philipp
AU - Cropet, Claire
AU - Caballero, Cristina
AU - Wolfrum-Ristau, Pia
AU - Satoh, Toyomi
AU - Vergote, Ignace
AU - Parma, Gabriella
AU - Nøttrup, Trine J
AU - Lebreton, Coriolan
AU - Fasching, Peter A
AU - Pisano, Carmela
AU - Manso, Luis
AU - Bourgeois, Hugues
AU - Runnebaum, Ingo
AU - Zamagni, Claudio
AU - Hardy-Bessard, Anne-Claire
AU - Schnelzer, Andreas
AU - Fabbro, Michel
AU - Schmalfeldt, Barbara
AU - Berton, Dominique
AU - Belau, Antje
AU - Lotz, Jean-Pierre
AU - Gropp-Meier, Martina
AU - Gladieff, Laurence
AU - Lück, Hans-Joachim
AU - Abadie-Lacourtoisie, Sophie
AU - Pujade-Lauraine, Eric
AU - Ray-Coquard, Isabelle
N1 - Wolfrum-Ristau: Department of Obstetrics and Gynecology, Paracelsus Medical University Salzburg, Salzburg, Austria; Lehr-kH Gynäkologie und
Geburtshilfe, RoMed Klinikum Rosenheim, Rosenheim, Germany
PY - 2023/12/21
Y1 - 2023/12/21
N2 - OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status.METHODS: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status.RESULTS: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk.CONCLUSION: This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.
AB - OBJECTIVE: In the PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab provided a substantial progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and homologous recombination deficiency (HRD)-positive tumors, irrespective of clinical risk. Subsequently, a clinically meaningful improvement in overall survival was reported with olaparib plus bevacizumab in the HRD-positive subgroup. We report updated progression-free survival and overall survival by clinical risk and HRD status.METHODS: Patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab received maintenance olaparib (up to 24 months) plus bevacizumab (up to 15 months in total) or placebo plus bevacizumab. This post hoc analysis evaluated 5-year progression-free survival and mature overall survival in patients classified by clinical risk and HRD status.RESULTS: Of 806 randomized patients, 74% were higher-risk and 26% were lower-risk. In higher-risk HRD-positive patients, the hazard ratio (HR) for progression-free survival was 0.46 (95% confidence interval (95% CI) 0.34 to 0.61), with 5-year progression-free survival of 35% with olaparib plus bevacizumab versus 15% with bevacizumab alone; and the HR for overall survival was 0.70 (95% CI 0.50 to 1.00), with 5-year overall survival of 55% versus 42%, respectively. In lower-risk HRD-positive patients, the HR for progression-free survival was 0.26 (95% CI 0.15 to 0.45), with 5-year progression-free survival of 72% with olaparib plus bevacizumab versus 28% with bevacizumab alone; and the HR for overall survival was 0.31 (95% CI 0.14 to 0.66), with 5-year overall survival of 88% versus 61%, respectively. No benefit was seen in HRD-negative patients regardless of clinical risk.CONCLUSION: This post hoc analysis indicates that in patients with newly diagnosed advanced HRD-positive ovarian cancer, maintenance olaparib plus bevacizumab should not be limited to those considered at higher risk of disease progression. Five-year progression-free survival rates support long-term remission and suggest an increased potential for cure with particular benefit suggested in lower-risk HRD-positive patients.
U2 - 10.1136/ijgc-2023-004995
DO - 10.1136/ijgc-2023-004995
M3 - Original Article (Journal)
C2 - 38129136
SN - 1048-891X
JO - INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
JF - INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
ER -