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Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil–tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial

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Abstract

Background

Pathological stage (pStage) and histological subtype are strong determinants of the treatment strategy for non-small cell lung cancer (NSCLC). Setouchi Lung Cancer study Group (SLCG) recently reported the results of a multicenter trial (SLCG0401) indicating that paclitaxel plus carboplatin (CBDCA/PTX) as adjuvant chemotherapy does not yield better survival than uracil–tegafur (UFT) in NSCLC patients with pStage IB–IIIA disease, while stratified analyses considering the pStage and histological subtype have not been performed.

Methods

We reanalyzed the overall survival (OS) and relapse-free survival (RFS) in 402 patients who had been randomly assigned to receive CBDCA/PTX or UFT by multivariate analysis with adjustments for the pStage and histological subtype.

Results

There were no significant differences in the OS or RFS between the two treatment settings either in the entire cohort (n = 402) and in some of subsets: pStage IB (n = 228), pStage II (n = 117), adenocarcinoma (AD, n = 265), and squamous cell carcinoma (SQ, n = 101). In pStage IIIA patients (n = 57), CBDCA/PTX yielded superior RFS to UFT [hazard ratio (HR) 0.44; P = 0.016]. Among the patients with non-AD and non-SQ histology (n = 36), UFT yielded both superior OS and RFS to CBDCA/PTX (HRs 0.16 and 0.23; P = 0.046 and 0.011, respectively).

Conclusions

There are subsets of patients in which one or the other between UFT and CBDCA/PTX is significantly more effective. Selection of adjuvant therapy for NSCLC patients needs to be made taking into consideration the pStage and histological subtype.

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Acknowledgements

This work is supported, in part, by a non-profit organization Epidemiological and Clinical Research Information Network (ECRIN). We thank all 40 hospitals and institutions for their participation and cooperation for enrollment of patient and data collection for the original study (SLCG0401) (alphabetical order): Aichi Cancer Center Research Institute, Ako Central Hospital, Chugoku Central Hospital, Hiroshima City Asa Citizens Hospital, Hiroshima University Hospital, Japanese Red Cross Society Himeji Medical Center, Japanese Red Cross Wakayama Medical Center, Kagawa Prefectural Central Hospital, Kagawa Rosai Hospital, Kawasaki Medical School Hospital, Kawasaki Medical School Kawasaki Hospital, Kishiwada City Hospital, Kochi Health Sciences Center, Kurashiki Central Hospital, Kurashiki Daiichi Hospital, Kure Kyosai Hospital, Kurume University Hospital, Kyoto University Hospital, Mitoyo General Hospital, Nagasaki Harbor Medical Center City Hospital, National Hospital Organization Iwakuni Clinical Center, National Hospital Organization Kure Medical Center, National Hospital Organization Kyushu Cancer Center, National Hospital Organization Matsue Medical Center, National Hospital Organization Minami-Okayama Medical Center, National Hospital Organization Nagara Medical Center, National Hospital Organization Okayama Medical Center, National Hospital Organization Shikoku Cancer Center, National Hospital Organization Yamaguchi-Ube Medical Center, Okayama Red Cross General Hospital, Okayama Saiseikai General Hospital, Okayama University Hospital, Osaka City General Hospital, Saiseikai Noe Hospital, Shimada Municipal Hospital, Shimane University Hospital, Tottori University Hospital, Toyota Kosei Hospital, Tsuyama Chuo Hospital, and Uwajima City Hospital

Funding

This study is supported in part by an operating expense of department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.

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Authors and Affiliations

  1. Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Junichi Soh & Shinichi Toyooka

  2. Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan

    Norihito Okumura

  3. Division of General Thoracic Surgery, Tottori University Hospital, Yonago, Japan

    Hiroshige Nakamura

  4. Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Japan

    Masao Nakata

  5. Department of Thoracic Surgery, Shikoku Cancer Center, Matsuyama, Japan

    Motohiro Yamashita

  6. Tokai Central Hospital, Kakamigahara, Japan

    Junichi Sakamoto

  7. Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu, Japan

    Motoi Aoe

  8. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan

    Katsuyuki Hotta

  9. Department of Biomedical Statistics and Bioinformatics, Kyoto University, Kyoto, Japan

    Satoshi Morita

  10. Department of Thoracic Surgery, Kyoto University, Kyoto, Japan

    Hiroshi Date

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  1. Junichi Soh
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Corresponding author

Correspondence to Junichi Soh.

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Conflict of interest

The following authors received research grants from companies: AstraZeneca (KH), Ono Pharmaceutical (KH), Chugai Pharmaceutical (ST and KH), Boehringer-Ingelheim (ST and KH), Astellas (KH), Novartis (KH), Bristol-Myers Squibb (KH), Eli Lilly Japan (KH) and MSD (KH). The following authors received personal fees from companies: Taiho Pharmaceutical (ST, NO, KH, SM and HD), Tsumura & CO (J. Sakamoto), Takeda Pharmaceutical (J. Sakamoto), Chugai Pharmaceutical (J. Sakamoto and KH), AstraZeneca (KH), Ono Pharmaceutical (KH), Boehringer-Ingelheim (KH), Nihon Kayaku (KH and J. Sakamoto), Novartis (KH), Bristol-Myers Squibb (KH and SM), Eli Lilly Japan (KH) and MSD (KH). All the other authors declared no conflicts of interest regarding this study.

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Soh, J., Toyooka, S., Okumura, N. et al. Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil–tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial. Int J Clin Oncol 24, 1367–1376 (2019). https://doi.org/10.1007/s10147-019-01508-9

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