Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial

Reiko Matsuzawa; Masahiro Morise; Kentaro Ito; Osamu Hataji; Kosuke Takahashi; Junji Koyama; Yachiyo Kuwatsuka; Yasuhiro Goto; Kazuyoshi Imaizumi; Hidetoshi Itani; Teppei Yamaguchi; Yoshitaka Zenke; Masahide Oki; Makoto Ishii

doi:10.1016/j.eclinm.2023.102303

Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial

EClinicalMedicine. 2023 Nov 10:66:102303. doi: 10.1016/j.eclinm.2023.102303. eCollection 2023 Dec.

Authors

Affiliations

¹ Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
³ Department of Respiratory Medicine, Matsusaka Municipal Hospital, Matsusaka, Japan.
⁴ Department of Respiratory Medicine, Anjo Kosei Hospital, Anjo, Japan.
⁵ Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan.
⁶ Department of Respiratory Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
⁷ Department of Respiratory Medicine, Japanese Red Cross Ise Hospital, Ise, Japan.
⁸ Department of Respiratory Medicine, National Cancer Center East, Kashiwa, Japan.
⁹ Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.

Abstract

Background: Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported.

Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60 mg/m² of DTX and 10 mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and β error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077.

Findings: Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42-79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n = 32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1-47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed.

Interpretation: DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options.

Funding: Eli Lilly Japan K.K.

Keywords: Docetaxel; First-line immune-therapy; Non-small cell lung cancer; Ramucirumab; Second-line treatments.