Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan.
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.
['Watanabe|Satoshi|S|', 'Yoshioka|Hiroshige|H|', 'Sakai|Hiroshi|H|', 'Hotta|Katsuyuki|K|', 'Takenoyama|Mitsuhiro|M|', 'Yamada|Kazuhiko|K|', 'Sugawara|Shunichi|S|', 'Takiguchi|Yuichi|Y|', 'Hosomi|Yukio|Y|', 'Tomii|Keisuke|K|', 'Niho|Seiji|S|', 'Yamamoto|Nobuyuki|N|', 'Nishio|Makoto|M|', 'Ohe|Yuichiro|Y|', 'Kato|Terufumi|T|', 'Takahashi|Toshiaki|T|', 'Kamada|Ami|A|', 'Suzukawa|Kazumi|K|', 'Omori|Yukie|Y|', 'Enatsu|Sotaro|S|', 'Nakagawa|Kazuhiko|K|', 'Tamura|Tomohide|T|']
D000328:Adult D000368:Aged D061067:Antibodies, Monoclonal, Humanized D000971:Antineoplastic Combined Chemotherapy Protocols D002289:Carcinoma, Non-Small-Cell Lung D002945:Cisplatin D003841:Deoxycytidine D005260:Female D006801:Humans D007564:Japan D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D011788:Quality of Life D016019:Survival Analysis D016896:Treatment Outcome
Necitumumab Gemcitabine Cisplatin Non-small cell lung cancer Japan