Efficacy of subsequent therapies in patients with advanced ovarian cancer who relapse after first-line olaparib maintenance: results of the PAOLA-1/ENGOT-ov25 trial
Philipp Harter, Christian Marth, Marie‐Ange Mouret‐Reynier, C. Cropet, D. Lorusso, E.M. Guerra-Alía, Takashi Matsumoto, Ignace Vergote, N. Colombo, Juhani Mäenpää, Coriolan Lebreton, N de Gregorio, A.M. Mosconi, María Jesús Rubio-Pérez, H. Bourgeois, PA Fasching, Sabrina Chiara Cecere, Anne‐Claire Hardy‐Bessard, Dominik Denschlag, Sixtine De Percin, Lars Hanker, L. Favier, Dirk Bauerschlag, Christophe Desauw, Peter Hillemanns, R. Largillier, J. Sehouli, Julien Grenier, E. Pujade-Lauraine, I. Ray-Coquard, Gerhard Bogner, Christian Marth, Edgar Petru, Alexander Reinthaller, Christian Schauer, Paul Sevelda, Lionel D’Hondt, Ignace Vergote, Peter Vuylsteke, Sakari Hietanen, Gabriel Lindahl, Johanna Mäenpää, Trine Jakobi Nøttrup, Ulla Puistola, Sophie Abadie-Lacourtoisie, Jérôme Alexandre, Dominique Berton-Rigaud, Emilie Boissier, Hugues Bourgeois, Annick Chevalier-Place, Pierre Combe, Cristina Costan, Jérôme Dauba, Laure De Cock, Christophe Desauw, Raymond Despax, Nadine Dohollou, Coraline Dubot, Michel Fabbro, Laure Favier, Anne Floquet, Philippe Follana, Claire Garnier Tixidre, Georges Garnier, Laurence Gladieff, Julien Grenier, Cécile Guillemet, Anne-Claire Hardy-Bessard, Florence Joly, Elsa Kalbacher, Marie-Christine Kaminsky, Jean-Emmanuel Kurtz, Rémy Largillier, Claudia Lefeuvre-Plesse, Anne Lesoin, Charles Briac Levache, Tifenn L’Haridon, Alain Lortholary, Jean-Pierre Lotz, Jacques Medioni, Jérôme Meunier, Mirerille Mousseau, Marie-Ange Mouret-Reynier, Patricia Pautier, Thierry Petit, Magali Provansal, Eric Pujade-Lauraine, Nadia Raban, Isabelle Ray-Coquard, Manuel Rodrigues, Frédéric Selle, Robert Sverdlin, Youssef Tazi, Benoît You, Bahriye Aktas, Dirk Olaf Bauerschlag, Thomas Beck, Antje Belau, Holger Bronger, Stefan Buchholz
Abstract
BACKGROUND: The use of first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is increasing in advanced ovarian cancer. Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments. We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance. PATIENTS AND METHODS: This post hoc analysis evaluated the efficacy of subsequent chemotherapy following disease progression by assessing time from FST to second subsequent therapy (SST) according to whether progression occurred during versus after first-line olaparib maintenance and FST type. A multivariate Cox model was used in the olaparib plus bevacizumab arm to identify prognostic factors influencing the efficacy of subsequent chemotherapy. RESULTS: Of 806 randomized patients, 544 (67.5%) progressed and received subsequent chemotherapy. The median time from FST to SST was shorter in patients in the olaparib plus bevacizumab arm who progressed during first-line olaparib maintenance (6.1 months) than in those who progressed after first-line olaparib maintenance (11.4 months). Multivariate analysis indicated that progression after (versus during) first-line olaparib maintenance influenced time from FST to SST (hazard ratio 0.65, 95% confidence interval 0.50-0.84; P = 0.0011) independently of platinum-free interval or clinical risk. Among patients who progressed and received platinum-based chemotherapy with a PARP inhibitor as FST, the efficacy of subsequent therapies was also dependent on whether progression occurred during versus after first-line olaparib maintenance. CONCLUSIONS: These results suggest that the timing of disease progression relative to first-line olaparib maintenance may impact the efficacy of subsequent platinum-based chemotherapy. Although results should be interpreted with caution, across all subgroups, including patients who received platinum-based chemotherapy with PARP inhibitor rechallenge as FST, the median time from FST to SST was longer if progression occurred after versus during first-line olaparib maintenance.