Satoshi Watanabe1, Hiroshige Yoshioka2, Hiroshi Sakai3, Katsuyuki Hotta4, Mitsuhiro Takenoyama5, Kazuhiko Yamada6, Shunichi Sugawara7, Yuichi Takiguchi8, Yukio Hosomi9, Keisuke Tomii10, Seiji Niho11, Nobuyuki Yamamoto12, Makoto Nishio13, Yuichiro Ohe14, Terufumi Kato15, Toshiaki Takahashi16, Ami Kamada17, Kazumi Suzukawa17, Yukie Omori17, Sotaro Enatsu17, Kazuhiko Nakagawa18, Tomohide Tamura19. 1. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 8050 Ikarashi 2-no-cho, Nishi-ku, Niigata, 950-2181, Japan. 2. Department of Respiratory Medicine, Kurashiki Central Hospital, 1 Chome-1-1 Miwa, Kurashiki, 710-8602, Japan. 3. Division of Thoracic Oncology, Saitama Cancer Center, 780 Komuro, Ina, Kitaadachi District, Saitama, 362-0806, Japan. 4. Department of Allergy and Respiratory Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital, 2 Chome-5-1 Shikatacho, Kita, Okayama, 700-8558, Japan. 5. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3 Chome-1-1 Notame, Minami Ward, Fukuoka, 811-1395, Japan. 6. Department of Internal Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka Prefecture, 830-0011, Japan. 7. Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirosemachi, Aoba Ward, Sendai, Miyagi Prefecture, 980-0873, Japan. 8. Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. 9. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3 Chome-18-22, Bunkyō-ku, Honkomagome, 113-0021, Tokyo, Japan. 10. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2 Chome-1-1 Minatojima Minamimachi, Chuo Ward, Kobe, Hyōgo Prefecture, 650-0047, Japan. 11. Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba-ken, 277-8577, Japan. 12. Third Department of Internal Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama Prefecture, 641-8509, Japan. 13. Department of Thoracic Medical Oncology, Japanese Foundation for Cancer Research, Cancer Institute Hospital, 3-8-31, Ariake, Koto, Tokyo, 135-8550, Japan. 14. Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. 15. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6 Chome-16-1 Tomiokahigashi, Kanazawa-ku, Yokohama-shi, Kanagawa, 236-0051, Japan. 16. Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. 17. Medical Affairs, Eli Lilly Japan K.K., 7-1-5 Isogamidori, Chuo-Ku, Kobe, 651-0086, Japan. 18. Department of Medical Oncology, Kindai University Faculty of Medicine, 3-4-1 Kowakae, Higashiosaka City, Osaka, 577-8502, Japan. 19. Thoracic Center, St. Luke's International Hospital, 9-1 Akashicho, Chuo-ku, Tokyo, 104-8560, Japan. Electronic address: tamuratomohide@gmail.com.
Abstract
OBJECTIVES: This open-label, multicenter, phase 1b/2 study assessed necitumumab plus gemcitabine and cisplatin (GC + N) in patients with previously untreated squamous non-small cell lung cancer in Japan. MATERIALS AND METHODS: The phase 1b part determined the gemcitabine dose for the phase 2 part, in which patients were randomized 1:1 to GC + N or gemcitabine and cisplatin (GC) (gemcitabine 1250 mg/m2 on days 1 and 8; cisplatin 75 mg/m2 on day 1 of maximum four 3-week cycles; nectimumab 800 mg on days 1 and 8 of a 3-week cycle continued until progressive disease or unacceptable toxicity). The primary endpoint of the phase 2 part was overall survival. RESULTS: In the phase 2 part, 181 patients received GC + N (N = 90) or GC (N = 91). Overall survival was significantly improved with GC + N versus GC (median, 14.9 months vs 10.8 months; hazard ratio [HR] = 0.66, 95% CI: 0.47 - 0.93, p = 0.0161). Improvements were also observed in progression-free survival (median, 4.2 months vs 4.0 months; HR = 0.56; p = 0.0004) and objective response rate (51% vs 21%; p < 0.0001). Survival was also significantly prolonged with GC + N versus GC for patients with epidermal growth factor receptor-positive tumors. Grade ≥3 treatment-emergent adverse events at ≥5% higher incidence with GC + N than GC were neutrophil count decreased (42% vs 35%), febrile neutropenia (12% vs 3%), decreased appetite (11% vs 4%), and dermatitis acneiform (6% vs 0%). CONCLUSION:GC + N is well tolerated and has significant and clinically meaningful treatment benefit in the first-line treatment of patients with squamous non-small cell lung cancer in Japan. Clinicaltrials.gov identifier: NCT01763788.
RCT Entities:
OBJECTIVES: This open-label, multicenter, phase 1b/2 study assessed necitumumab plus gemcitabine and cisplatin (GC + N) in patients with previously untreated squamous non-small cell lung cancer in Japan. MATERIALS AND METHODS: The phase 1b part determined the gemcitabine dose for the phase 2 part, in which patients were randomized 1:1 to GC + N or gemcitabine and cisplatin (GC) (gemcitabine 1250 mg/m2 on days 1 and 8; cisplatin 75 mg/m2 on day 1 of maximum four 3-week cycles; nectimumab 800 mg on days 1 and 8 of a 3-week cycle continued until progressive disease or unacceptable toxicity). The primary endpoint of the phase 2 part was overall survival. RESULTS: In the phase 2 part, 181 patients received GC + N (N = 90) or GC (N = 91). Overall survival was significantly improved with GC + N versus GC (median, 14.9 months vs 10.8 months; hazard ratio [HR] = 0.66, 95% CI: 0.47 - 0.93, p = 0.0161). Improvements were also observed in progression-free survival (median, 4.2 months vs 4.0 months; HR = 0.56; p = 0.0004) and objective response rate (51% vs 21%; p < 0.0001). Survival was also significantly prolonged with GC + N versus GC for patients with epidermal growth factor receptor-positive tumors. Grade ≥3 treatment-emergent adverse events at ≥5% higher incidence with GC + N than GC were neutrophil count decreased (42% vs 35%), febrile neutropenia (12% vs 3%), decreased appetite (11% vs 4%), and dermatitis acneiform (6% vs 0%). CONCLUSION:GC + N is well tolerated and has significant and clinically meaningful treatment benefit in the first-line treatment of patients with squamous non-small cell lung cancer in Japan. Clinicaltrials.gov identifier: NCT01763788.