Efficacy and Safety of Amrubicin Therapy After Chemoimmunotherapy in Small Cell Lung Cancer Patients

Kohei Kushiro; Satoshi Watanabe; Yuka Goto; Toshiya Fujisaki; Naohiro Yanagimura; Aya Ohtsubo; Satoshi Shoji; Koichiro Nozaki; Tomohiro Tanaka; Yu Saida; Yusuke Sato; Takeshi Ota; Jun Koshio; Yoshiki Hayashi; Takao Miyabayashi; Naoya Matsumoto; Kosuke Ichikawa; Kenichi Koyama; Toshiaki Kikuchi

Disclosures

Transl Lung Cancer Res. 2022;11(9):1858-1865. 

In This Article

Abstract and Introduction

Abstract

Background: Although the addition of immune checkpoint inhibitors (ICIs) to platinum-doublet chemotherapy has improved the efficacy of first-line therapy in extensive-disease small cell lung cancer (SCLC) patients, the best treatment option for patients with recurrent SCLC has not yet been determined. We conducted a retrospective study to evaluate the efficacy and safety of amrubicin (AMR) therapy after treatment with ICIs.

Methods: We retrospectively assessed patients with recurrent SCLC who received AMR after chemoimmunotherapy at the Niigata Lung Cancer Treatment Group from August 2019 to February 2021.

Results: This analysis included 30 patients. The median progression-free survival (PFS) and overall survival (OS) were 3.8 (95% CI: 2.7–4.2) and 10 (95% CI: 7.4–14.8) months, respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 (95% CI: 1.1–4.0) vs. 4.2 (95% CI: 2.3–4.8) months, P=0.1142, OS; 10.0 (95% CI: 5.2–14.8) vs. 10.4 (95% CI: 3.8–NE) months, P=0.5525]. The most common adverse event was grade ≥3 neutropenia, which occurred in 22 of 30 patients (73%), and 2 patients (7%) discontinued AMR due to adverse events.

Conclusions: AMR after chemoimmunotherapy shows good clinical efficacy and safety in patients with recurrent SCLC.

Introduction

Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers.[1] SCLC is a highly malignant tumor with a rapid growth rate and early lymph node and distant metastasis, but it is characterized by high sensitivity to radiotherapy and chemotherapy. For decades, the standard first-line chemotherapy for extensive-disease SCLC (ED-SCLC) has been platinum-doublet therapies, such as cisplatin (CDDP)/carboplatin plus irinotecan and CDDP/carboplatin plus etoposide (ETP), as no new drugs have been approved in the field of SCLC for approximately 20 years.[2,3] Recent clinical trials have shown that the addition of the programmed cell death ligand-1 (PD-L1) inhibitors atezolizumab and durvalumab to platinum and ETP significantly prolonged the survival time of patients.[4,5] Thus, the PD-L1 inhibitor plus platinum and ETP has become the standard first-line therapy for ED-SCLC.

Although SCLC is highly sensitive to first-line chemoimmunotherapy, most patients experience recurrence. The one-year progression-free rates after cisplatin plus irinotecan or cisplatin plus etoposide are only 8% and 12%, respectively.[2] The addition of PD-L1 inhibitors to platinum plus ETP have led to some improvement in progression-free survival (PFS) and overall survival (OS); however, the one-year survival rates remain low, at only 10% to 13%.[4,5] Because most patients with ED-SCLC require second-line therapy, a number of studies have been conducted to establish effective treatments for recurrent SCLC. Previous studies showed that nogitecan,[6] CDDP plus ETP plus irinotecan,[7] and amrubicin (AMR)[8] were effective treatment options for recurrent SCLC. Although patients with refractory SCLC respond poorly to chemotherapy, AMR has been shown to be effective, regardless of the mode of recurrence, and is a standard salvage treatment for recurrent SCLC.[9,10] In a meta-analysis of second-line AMR, the progression-free survival (PFS) rates at 3, 6, and 9 months were 63% (95% CI: 57–69%), 28% (95% CI: 21–35%), and 10% (95% CI: 6–14%), respectively.[11] However, all of the studies regarding second-line treatment for SCLC were performed before the approval of PD-L1 inhibitors, so standard second-line treatment options using PD-L1 inhibitor in combination with platinum and ETP still need to be established. In addition, the safety of AMR therapy after chemoimmunotherapy is not yet known. Moreover, in NSCLC, the efficacy of cytotoxic chemotherapy following immune checkpoint inhibitors (ICI) has increased.[12] Thus, in this study, we retrospectively evaluated the therapeutic effects and safety of AMR therapy in SCLC patients who experience recurrence after chemoimmunotherapy. We present the following article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-225/rc).

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