Randomized phase II study of chemoradiotherapy with cisplatin + S-1 versus cisplatin + pemetrexed for locally advanced non-squamous non-small cell lung cancer: SPECTRA study.

Objectives: SPECTRA is a multicenter, randomized phase II study of chemotherapy with cisplatin (CDDP) plus S-1 versus CDDP plus pemetrexed (PEM) in combination with thoracic radiotherapy (TRT) for locally advanced non-squamous non-small cell lung cancer, in order to determine which of these two regimens might be preferable for comparison with standard therapies in a future phase III study.
Materials and Methods: Patients were randomly assigned to receive CDDP + S-1 (CDDP 60 mg/m ² on day 1 and S-1 80 mg/m2 on days 1-14, every 4 weeks, up to 4 cycles) or CDDP + PEM (CDDP 75 mg/m ² + PEM 500 mg/m ² on day 1, every 3 weeks, up to 4 cycles) combined with TRT (60 Gy in 30 fractions). The primary endpoint was the 2-year progression-free survival (PFS) rate. The sample size had been set at 100 patients.
Results: A total of 102 patients were randomized to receive CDDP + S-1 or CDDP + PEM (CDDP + S-1, n = 52; CDDP + PEM, n = 50) between January 2013 and October 2016. The results in the CDDP + S1 group and CDDP + PEM group were as follows: completion rates of TRT (60 Gy)/chemotherapy (4 cycles) was 92 %/73 % and 98 %/86 %, respectively; the response rates were 60 % and 64 %, respectively; median PFS after a median follow-up of 32.1 months, 12.7/13.8 months (hazard ratio [HR] = 1.16; 95 % confidence interval [CI], 0.73-1.84); 2-year PFS rate, 36.5 % (95 % CI, 23.5-49.6)/32.1 % (95 %CI, 18.9-45.4); median OS, 48.3/59.1 months (HR = 1.05; 95 %CI, 0.58-1.90); 2-year OS rate, 69.2 % (95 %CI, 56.7-81.8)/66.4 % (95 %CI, 53.0-79.9); Grade 3 toxicities: febrile neutropenia (12 %/2 %), anorexia (8 %/16 %), diarrhea (8 %/0 %), esophagitis (6 %/8 %), and neutropenia (35 %/50 %); Grade 2 or worse radiation pneumonitis, 15 % (8 patients)/4 % (2 patients).
Conclusion: The 2-year PFS rate in the CDDP + S-1 arm was higher than that in the CDDP + PEM arm. Both treatments were safe, with manageable toxicities.
Competing Interests: Declaration of Competing Interest S.N. reports grants and personal fees from AstraZeneca, Chugai, Taiho, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Shionogi, and Yakult, grants and personal fees from Pfizer, MSD, and Eli Lilly, grants from Merck Serono, outside the submitted work. T.Y. reports personal fees from Chugai, Boehringer Ingelheim, AstraZeneca, and Bristol‐Myers Squibb, outside the submitted work. K.S. reports personal fees from Chugai, Ono, Novartis, and Taiho, outside the submitted work. A.O. reports personal fees from Taiho, Ono, Chugai, Novartis, AstraZeneca, and MSD, outside the submitted work. T.S reports grants and personal fees from Astellas, AstraZeneca, Chugai, Eli Lilly, Kissei, MSD, Boehringer Ingelheim, Novartis, Pfizer, and Takeda, personal fees from Bristol-Myers Squibb, Kyowa Hakko Kirin, Nippon Kayaku, Ono, Roche, Taiho, Thermo Fisher Scientific, and Yakult, grants from Bayer, Daiichi Sankyo, Eisai, LOXO Oncology, Merck Serono, outside the submitted work. M.N. reports grants and non-financial support from F. Hoffmann-La Roche, during the conduct of the study; grants and personal fees from Ono, Bristol-Myers Squibb, Pfizer, Chugai, Eli Lilly, Taiho, AstraZeneca, MSD, Novartis, personal fees from Boehringer-Ingelheim, Sankyo Healthcare, Taiho, Merck Serono, grants from Astellas, outside the submitted work. N.Y. reports grants and personal fee from Chugai, Eisai, Eli Lilly, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Ono, and Takeda, grants from Taiho, Quintiles, Astellas, Novartis, Daiichi-Sankyo, Kyowa-Hakko Kirin, Bayer, Janssen Pharma, MSD, and Merck, personal fees from AstraZeneca, Otsuka, Cimic, and Sysmex, outside the submitted work. T.H. reports grants and personal fees from Ono, Chugai, AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Kissei, Taiho, Pfizer, Clovis Oncology, MSD, and Ignyta, grants from Merck Serono, Eisai, Takeda, Dainippon Sumitomo, Abbvie, Kyowa Hakko Kirin, Daiichi Sankyo, Astellas, Servier, Janssen, outside the submitted work. H.O. reports grants from Takeda, MSD, Ono, AstraZeneca, Merck, Chugai, Taiho, Bristol-Myers Squibb, Eli Lilly, Daiich Sankyo, outside the submitted work. T.K. reports grants and personal fee from AstraZeneca, MSD, and Chugai, personal fees from Eli Lilly, Ono, Bristol-Myers Squibb, and Boehringer Ingelheim, outside the submitted work. M.S. reports grants and personal fees from Chugai, Eli Lilly, Pfizer, AstraZeneca, Bristol-Myers Squibb, Ono, MSD, and Novartis, grants from Takeda, AbbVie, Ignyta, and Loxo Oncology, personal fees from Taiho, and Boehringer Ingelheim, outside the submitted work. K.G. reports grants and personal fees from Taiho, Chugai, Ono, AstraZeneca, Bristol-Myers Squibb, MSD, DAIICHI SANKYO, Pfizer, Novartis, Takeda, Eli Lilly, Merck Serono, Boehringer Ingelheim, RIKEN GENESIS, AbbVie, and Life Technologies, grants from Sumitomo Dainippon, Astellas, Eisai, Kyowa Hakko Kirin, Ignyta, Janssen, Loxo Oncology, Sysmex Corporation, and Oxonc, personal fees from F.Hoffmann-La Roche, SRL, and Nippon Kayaku, outside the submitted work. T.Y. reports grants and personal fees from Takeda, Chugai, Boehringer Ingelheim, Daiichi-Sankyo, and Bayer, grants from Ono, Merck Serono, Astellas, and Eli Lilly, personal fees from Taiho, Pfizer, Sysmex, Huya Biosciences, and Gilead Sciences, outside the submitted work. Y.O. reports grants and personal fees from Lilly, Bristol-Myers Squibb, Taiho, AstraZeneca, Chugai, ONO, Pfizer, MSD, Kyorin, Takeda, Novartis, AbbVie, grants from Amgen, Boehringer Ingelheim, LOXO, and Janssen, personal fees from Celltrion, outside the submitted work. T.A. declares no conflict of interest.
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