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A study of second-line irinotecan plus cisplatin vs. irinotecan alone in platinum-naïve patients with early relapse of gastric cancer refractory to adjuvant S-1 monotherapy: exploratory subgroup analysis of the randomized phase III TRICS trial

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Abstract

Backgrounds

Many patients with gastric cancer relapse during or early after adjuvant chemotherapy. The standard treatment for early relapse patients is a second-line chemotherapy (SLC) based on irinotecan, taxanes, or a platinum-based chemotherapy. The platinum-containing biweekly irinotecan plus cisplatin (IRI/CDDP) combination was assumed to be promising in several reports of clinical trials as SLC. TRICS trial, a randomized phase III study of IRI/CDDP vs. IRI in platinum-naïve gastric cancers refractory to S-1 monotherapy, revealed that both irinotecan-based chemotherapies were effective and well tolerated.

Methods

This study analyzed 108 patients in the TRICS trial who experienced early relapse. Patients receiving IRI/CDDP (IRI, 60 mg/m2; CDDP, 30 mg/m2, q2w) versus IRI (150 mg/m2, q2w) were compared regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety.

Results

The OS was 14.0 (95% confidence interval [CI]: 11.0–21.2) and 14.0 (95% CI: 10.7–16.5) months for IRI/CDDP and IRI, respectively (hazard ratio [HR]: 0.782; 95% CI: 0.515–1.188, P = 0.249). No significant differences were observed for PFS (5.0 vs. 4.5 months, respectively; HR: 0.802; 95% CI: 0.543–1.185, P = 0.268) or ORR (19.6% [95% CI: 9.4–33.9%] vs. 23.3% [95% CI: 11.8–38.6%], respectively). The incidence of grade 3–4 anemia was higher for IRI/CDDP than for IRI (20% vs. 0%, respectively; P = 0.0006).

Conclusion

Our study showed no significant survival differences between IRI/CDDP and IRI in platinum-naïve patients who relapsed during or within 6 months after S-1 adjuvant therapy; therefore, IRI may be a good option in this population.

Clinical trial information

UMIN 000002571.

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Acknowledgements

We thank the investigators who enrolled patients in this trial. Furthermore, we deeply appreciate all patients who participated in the trial. This work was supported in part by the non-profit organization Epidemiological & Clinical Research Information Network (ECRIN).

Funding

This work was supported, in part, by the non-profit organization Epidemiological & Clinical Research Information Network (ECRIN). [No grant numbers apply].

Author information

Authors and Affiliations

  1. Department of Surgery, National Hospital Organization Osaka National Hospital, 2-1-14, Houenzaka, Chuo-ku, Osaka, 540-0006, Japan

    Kazuhiro Nishikawa

  2. Biostatistics Center, Graduate School of Medicine, Kurume University, 67 Asahi-Machi, Kurume, Fukuoka, 830-0011, Japan

    Kenta Murotani

  3. Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka, 558-0056, Japan

    Kazumasa Fujitani

  4. Department of Surgery, Inagaki Clinic, 1-2-9, Nenohanacho, Owariasahi, 488-0002, Japan

    Hitoshi Inagaki

  5. Department of Surgery, Ikeda Municipal Hospital, 3-1-18 Jonan, Ikeda, 563-8510, Japan

    Yusuke Akamaru

  6. Department of Medical Oncology, Osaka City General Hospital, 2-13-22, Miyakojimahondori, Miyakojima-ku, Osaka, 534-0021, Japan

    Shinya Tokunaga

  7. Department of Surgery, Shizuoka General Hospital, 4-27-1, Kitaando, Aoi-ku, Shizuoka, 420-0881, Japan

    Masakazu Takagi

  8. Department of Surgery, Yao Municipal Hospital, 1-3-1, Ryugecho, Yao, 581-0069, Japan

    Shigeyuki Tamura

  9. Department of Medical Oncology, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan

    Naotoshi Sugimoto

  10. Department of Gastroenterology, Saiseikai Shiga Prefectural Hospital, 2-4-1, Ohashi, Ritto, 520-3046, Japan

    Tadashi Shigematsu

  11. Department of Gastric Surgery, The National Hospital Organization National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Takaki Yoshikawa

  12. Department of Digestive Tract and General Surgery, Saitama Medical Center, 1981 Kamoda, Kawagoe, 350-0844, Japan

    Tohru Ishiguro

  13. Comprehensive Cancer Center, Aizawa Hospital, 2-5-1, Honjo, Matsumoto, 390-0814, Japan

    Masato Nakamura

  14. Department of Gastroenterology, National Hospital Organization Osaka National Hospital, 2-1-14, Houenzaka, Chuo-ku, Osaka, 540-0006, Japan

    Hiroko Hasegawa

  15. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54, Shogoinkawaharacho, Sakyo-ku, Kyoto, 606-8397, Japan

    Satoshi Morita

  16. Data Center, Epidemiological and Clinical Research Information Network, 21-7, Shogoinsannocho, Sakyo-ku, Kyoto, 606-8392, Japan

    Yumi Miyashita

  17. Department of Surgery, Ozawa Hospital, 1-1-17, Honcho, Odawara, 250-0012, Japan

    Akira Tsuburaya

  18. Tokai Central Hospital, 4-6-2, Higashijimacho Sohara, Kakamigahara, 504-8601, Japan

    Junichi Sakamoto

  19. Kaizuka City Hospital, 3-10-20, Hori, Kaizuka, 597-0015, Japan

    Toshimasa Tsujinaka

Authors
  1. Kazuhiro Nishikawa
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  2. Kenta Murotani
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  3. Kazumasa Fujitani
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  4. Hitoshi Inagaki
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  6. Shinya Tokunaga
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  7. Masakazu Takagi
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  8. Shigeyuki Tamura
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  9. Naotoshi Sugimoto
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  11. Takaki Yoshikawa
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  15. Satoshi Morita
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  16. Yumi Miyashita
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  17. Akira Tsuburaya
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  18. Junichi Sakamoto
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  19. Toshimasa Tsujinaka
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Corresponding author

Correspondence to Kazuhiro Nishikawa.

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Conflict of interest

Kazuhiro Nishikawa has received honoraria from Chugai, Taiho, Yakult, Eli Lilly, Tsumura, and EA Pharma, and research funding from Yakult and Taiho, outside the submitted work. Takaki Yoshikawa has received lecture fees from Chugai, Taiho, Yakult, Eli Lilly and Ono, and for advisory work for Ono and MSD, outside the submitted work. Masato Nakamura has received honoraria from Chugai, Taiho, Merk, Takeda, Yakult, Eli Lilly, Bayer, Ono, and Otsuka Pharma, outside the submitted work. Satoshi Morita has received honoraria from Chugai and Taiho, outside the submitted work. Junichi Sakamoto has received consultant fee from Takeda, and Honoraria from Tsumura, Nihon Kayaku, and Chugai, outside the submitted work. All remaining authors have declared no conflicts of interest to declare.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Nishikawa, K., Murotani, K., Fujitani, K. et al. A study of second-line irinotecan plus cisplatin vs. irinotecan alone in platinum-naïve patients with early relapse of gastric cancer refractory to adjuvant S-1 monotherapy: exploratory subgroup analysis of the randomized phase III TRICS trial. Cancer Chemother Pharmacol 83, 867–874 (2019). https://doi.org/10.1007/s00280-019-03802-9

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