Efficacy and safety of amrubicin therapy after chemoimmunotherapy in small cell lung cancer patients

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 months (95% CI: 2.7-4.2) and 10 months (95% CI: 7.4-14.8), respectively. The median PFS and OS did not significantly differ between the sensitive and refractory groups [PFS; 3.1 months (95% CI:1.1-4.0) vs. 4.2 months (95% CI: 2.3-4.8), P=0.1142, OS; 10.0 months (95% CI: 5.2-14.8) vs. 10.4 months (95% CI: 3.8-NE), 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.

Impact of immune‐related adverse events on survival outcomes in extensive‐stage small cell lung cancer patients treated with immune checkpoint inhibitors

“…The IMPOWER133 trial showed that adding ICIs to carboplatin and etoposide improved survival in patients with ES‐SCLC compared to chemotherapy alone 21 . However, other trials failed to show any benefit of ICIs as a second‐line treatment for ES‐SCLC 22–25 . Thus, it seems that the efficacy of ICIs is mainly observed during the first‐line treatment and that subsequent ICI therapy may not be effective for patients who did not respond to first‐line ICI plus chemotherapy.…”

“… 21 However, other trials failed to show any benefit of ICIs as a second‐line treatment for ES‐SCLC. 22 , 23 , 24 , 25 Thus, it seems that the efficacy of ICIs is mainly observed during the first‐line treatment and that subsequent ICI therapy may not be effective for patients who did not respond to first‐line ICI plus chemotherapy. Therefore, it is crucial to identify biomarkers that can predict the response to first‐line ICI plus chemotherapy and guide the selection of patients who may benefit from this treatment.…”

Phase II study of IRInotecan treatment after COmbined chemo‐immunotherapy for extensive‐stage small cell lung cancer: Protocol of IRICO study

“…In our previous study, the sequence of chemotherapy following nivolumab in non‐small cell lung cancer enhanced the antitumor activity of cytotoxic chemotherapy. 18 In addition, a recent retrospective study revealed that the efficacy of AMR therapy after chemo‐immunotherapy in patients with SCLC showed an overall response rate of 47% (95% confidence interval [CI]: 30%–64%), and the disease‐control rate of 73% (95% CI: 56%–86%), 19 indicating that single agent of AMR is a useful treatment option after chemo‐immunotherapy. Irinotecan is a topoisomerase I inhibitor and a major chemotherapeutic agent and has been used for treating SCLC for a long time.…”

Extensive-Stage Small-Cell Lung Cancer: Current Landscape and Future Prospects

“…Several retrospective studies have assessed the efficacy and safety of AMR for relapsed SCLC after a first-line regimen, including ICI. [50][51][52] An ORR of 47%, median PFS of 3.8 months, and median OS of 10 months was reported. Toxicity was manageable; 73% of patients had grade 3 or 4 neutropenia and only one case (3%) of interstitial lung disease resulting in discontinuation of AMR.…”

“…Toxicity was manageable; 73% of patients had grade 3 or 4 neutropenia and only one case (3%) of interstitial lung disease resulting in discontinuation of AMR. 52 …”