Efficacy and safety of amrubicin monotherapy after atezolizumab plus carboplatin and etoposide in patients with relapsed small-cell lung cancer

Abstract

This study examined the activity and safety of amrubicin monotherapy among relapsed small-cell lung cancer (SCLC) patients who had previously been treated with atezolizumab plus carboplatin and etoposide (AteCE). This retrospective study evaluated patients with relapsed SCLC who were treated with previously AteCE combination therapy followed by amrubicin monotherapy between August 2019 and May 2021. Clinical efficacy and toxicity were analyzed. Overall, 40 patients were included: 12 and 28 patients had sensitive and refractory relapse, respectively. The response rate was 32.5% (25.0% in the sensitive group and 35.7% in the refractory group). The median progression-free survival (PFS) and overall survival (OS) from the first amrubicin treatment was 3.4 months (95% CI: 1.9–4.9 months) and 9.9 months (95% CI: 4.5–11.5 months), respectively. There was no significant between-group difference in median PFS (3.6 months vs. 3.2 months, p = 0.42) or median OS (11.2 months vs. 7.3 months, p = 0.78). Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52.5% of patients; decreased neutrophil count in 57.5%; and febrile neutropenia in 10.0%. Grade 3 pneumonitis was observed in one patient. There were no treatment-related deaths. Amrubicin is feasible and effective for relapsed SCLC patients previously treated with AteCE therapy. Although immune checkpoint inhibitor treatment (ICI) does not improve the effect of amrubicin, the toxicity is not increased, suggesting that amrubicin remains effective even after ICI administration. Thus, amrubicin after AteCE could be the preferred standard chemotherapeutic choice in patients with relapsed SCLC.

Metastatic small cell bladder cancer treated with sequential systemic therapy including pembrolizumab and amrubicin: A case report

“…Some studies have reported the efficacy and safety of AMR after administration of ICIs in patients with SCLC. These studies also revealed that the incidence of severe toxicities associated with AMR did not increase following treatment with ICIs 6,11,12 . Moreover, a recent study reported the efficacy of combination Pem and AMR therapy as second‐line treatment for SCLC, including median OS of 10.6 months and median PFS of 4.0 months 13 .…”

Relationship between immune‐related adverse events and treatment effectiveness in extensive disease small cell lung cancer

“…Although no phase 3 study previously evaluated the efficacy of amrubicin in combination with platinum doublet and ICI therapy in ED‐SCLC, a study reported a median OS of 11.7 months in sensitive relapse and 7.3 months in refractory relapse after treatment with atezolizumab plus carboplatin and etoposide 13 . These data indicate that amrubicin is an effective and feasible second‐line treatment option.…”

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.…”