• Martin Dreyling, Armando Santoro, Luigina Mollica, Sirpa Leppä, George A Follows, Georg Lenz, Won Seog Kim, Arnon Nagler, Panayiotis Panayiotidis, Judit Demeter, Muhit Özcan, Marina Kosinova, Krimo Bouabdallah, Franck Morschhauser, Don A Stevens, David Trevarthen, Marius Giurescu, Lisa Cupit, Li Liu, Karl Köchert, Henrik Seidel, Carol Peña, Shuxin Yin, Florian Hiemeyer, Jose Garcia-Vargas, Barrett H Childs, and Pier Luigi Zinzani.
• Martin Dreyling, Ludwig Maximilians University of Munich, Munich; Georg Lenz, University Hospital Münster, Münster; Marius Giurescu, Karl Köchert, Henrik Seidel, and Florian Hiemeyer, Bayer AG, Berlin, Germany; Armando Santoro, Humanitas Clinical and Research Center, Rozzano; Pier Luigi Zinzani, University of Bologna, Bologna, Italy; Luigina Mollica, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Sirpa Leppä, Helsinki University Central Hospital Cancer Center, Helsinki, Finland; George A. Follows, Addenbrooke's Hospital, Cambridge, United Kingdom; Won Seog Kim, Samsung Medical Center, Seoul, South Korea; Arnon Nagler, Tel Aviv University, Tel HaShomer, Israel; Panayiotis Panayiotidis, National and Kapodistrian University of Athens, Athens, Greece; Judit Demeter, Semmelweis University, Budapest, Hungary; Muhit Özcan, Ankara University School of Medicine, Ankara, Turkey; Marina Kosinova, Kemerovo Regional Clinical Hospital, Kemerovo, Russian Federation; Krimo Bouabdallah, University Hospital of Bordeaux, Pessac; Franck Morschhauser, Hôpital Claude Huriez, Lille, France; Don A. Stevens, Norton Cancer Institute, Louisville, KY; David Trevarthen, Comprehensive Cancer Care and Research Institute of Colorado, Englewood, CO; and Lisa Cupit, Li Liu, Carol Peña, Shuxin Yin, Jose Garcia-Vargas, and Barrett H. Childs, Bayer HealthCare Pharmaceuticals, Whippany, NJ.
• J. Clin. Oncol. 2017 Dec 10; 35 (35): 3898-3905.

AbstractPurpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.

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