JTO Clinical and Research Reports (May 2023)

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan

  • Yasushi Goto, MD, PhD,
  • Hirotsugu Kenmotsu, MD, PhD,
  • Motohiro Tamiya, MD,
  • Shuji Murakami, MD,
  • Takayasu Kurata, MD,
  • Noriko Yanagitani, MD,
  • Hirokazu Taniguchi, MD, PhD,
  • Shoichi Kuyama, MD, PhD,
  • Junichi Shimizu, MD, PhD,
  • Toshihide Yokoyama, MD,
  • Naoko Shimada, MD, PhD,
  • Tadashi Maeda, MD,
  • Akihiro Tamiya, MD,
  • Ayumi Uchiyama, MD,
  • Kazuyoshi Imaizumi, MD,
  • Takayuki Takahama, MD, PhD,
  • Terufumi Kato, MD,
  • Hidetoshi Hayashi, MD, PhD,
  • Naoko Shiraiwa, MSc,
  • Shigeyuki Toyoizumi, MSc,
  • Hironori Kikkawa, PhD,
  • Despina Thomaidou, MSc,
  • Makoto Nishio, MD, PhD

Journal volume & issue
Vol. 4, no. 5
p. 100508

Abstract

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Introduction: Lorlatinib is an ALK tyrosine kinase inhibitor approved in Japan for the treatment of advanced ALK+ NSCLC. There has been little evidence about lorlatinib efficacy after first-line (1L) alectinib in clinical practice in Japan. Methods: We retrospectively analyzed patients with advanced ALK+ NSCLC previously treated with 1L alectinib at multiple sites in Japan. Primary objectives were to collect patient demographics at baseline and estimate time to treatment failure (TTF) with second-line (2L) or third-line (3L) or later line (≥3L) lorlatinib treatment. Secondary objectives included objective response rate (ORR) with lorlatinib, reason for discontinuation and time to last treatment failure with lorlatinib, TTF and ORR of alectinib, and combined TTF. Results: Among the 51 patients included in the study, 29 (56.9%) received 2L and 22 (43.1%) received ≥3L lorlatinib treatment. At lorlatinib initiation, brain metastases were reported in 25 patients (49.0%), and 32 (62.7%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Median TTF with lorlatinib was 11.1 months (95% confidence interval [CI]: 4.6–13.8) in any line, 10.8 months (95% CI: 3.9–13.8) in 2L, and 11.5 months (95% CI: 2.9–not reached) in ≥3L. Median TTF was 11.5 months (95% CI: 3.9–not reached) in patients with brain metastases at lorlatinib initiation and 9.9 months (95% CI: 4.3–13.8) in patients without brain metastases. ORR was 35.7% with any-line lorlatinib treatment. Conclusions: Patient characteristics and efficacy were comparable with previous reports when lorlatinib was given after 1L alectinib in patients with ALK+ NSCLC.

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