MedicalResearch.com Interview with:
Junzo Hamanishi M.D., Ph.D.
Department of Gynecology and Obstetrics,
Kyoto University Graduate School of Medicine
Medical Research: What is the background for this study?
Dr. Hamanishi: More than 70% of patients with advanced ovarian cancer who achieve remission ultimately relapse and there are few effective treatments for these patients. Because the development of new treatment strategies for these patients is urgently required, we have focused on and studied the potential of cancer cells to escape from host immunity with PD-1/PD-L1 immunosuppressive signal in the tumor microenvironment to find new treatment strategies to overcome this phenomenon, collaborating with Professor Honjo who discovered PD-1 since 2006. Therefore, we conducted a phase II clinical trial in 20 platinum-resistant, recurrent ovarian cancer patients to evaluate the safety and anti-tumor efficacy of anti-PD-1 antibody (nivolumab) with 2 cohort at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts).
Medical Research: What are the main findings?
Dr. Hamanishi: This study is the first investigator-initiated phase II clinical trial testing the safety and efficacy of nivolumab against platinum-resistant ovarian cancer. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, including two patients with a durable complete response (3mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival was 3.5 months, with a median overall survival of 20.0 months. Especially in the 3 mg/kg cohort, two patients achieved a complete response, and disease stabilized in another two patients. The objective response rate in 3mg/kg cohort cohort was 20% and disease was controlled in 40% of the higher-dose group. In the four patients who demonstrated an antitumor response, responses were durable and evident. Grade 3 or 4 treatment-related adverse events (AE) occurred in eight out of 20 patients or 40% overall. However, the frequency of AEs were not different in 2 cohorts.
Medical Research: What should clinicians and patients take away from your report?
Dr. Hamanishi: From our study, we showed nivolumab has enough activity in platinum-resistant ovarian cancer and merit to conduct further investigation in larger-scale clinical trials to confirm our data and to get pharmaceutical approval for ovarian cancer.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Hamanishi: While we showed that nivolumab has something potential activity in platinum-resistant ovarian cancer, the objective response rate was not so high. Thus predictive biomarkers related to antitumor effect or severe side effect of nivolumab treatment are urgently required to enlarge new treatment modality including combination therapy with nivolumab for ovarian cancers. And we have tried to find these markers.
Junzo Hamanishi, Masaki Mandai, Takafumi Ikeda, Manabu Minami,Atsushi Kawaguchi, Toshinori Murayama, Masashi Kanai, Yukiko Mori,Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko,Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Satoshi Morita Masayuki Yokode, Akira Shimizu, Tasuku Honjo, and Ikuo Konishi
Junzo Hamanishi M.D., Ph.D. (2015). Nivolumab Has Potential Activity Against Platinum Resistant Ovarian Cancer MedicalResearch.com