Sacituzumab govitecan: a new hope for patients with pretreated extensive small-cell lung cancer (SCLC)—insights from the TROPiCS-03 trial

Abstract

Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is associated with a poor prognosis (1). While immunotherapies and targeted therapies have transformed the treatment of non-small-cell lung cancer (NSCLC) (2,3), little progress has been made in the treatment of extensive SCLC over the past three decades, with platinum-etoposide regimens still remaining the cornerstone of treatment (4,5). Over the past few years, the addition of immune checkpoint inhibitors (ICIs) to first-line platinum-etoposide chemotherapy showed a modest but significant improvement in overall survival (OS) (6,7). Despite SCLC’s initial strong response to chemotherapy, most patients experience relapse within six months. Second-line treatment is determined by the treatment-free interval (TFI) and the response to first-line platinum-based chemotherapy (4,5). Platinum-etoposide rechallenge is recommended for platinum-sensitive SCLC (TFI ≥3 months), as it yields a high objective response rate (ORR) of 49% and is associated with better clinical outcomes compared to alternative chemotherapy regimens (8). In contrast, for platinum-refractory (progression during platinum chemotherapy) or platinum-resistant disease (TFI <3 months), outcomes are poor, with second-line chemotherapy achieving a very low ORR of approximately 15% (5). Topotecan, a topoisomerase I inhibitor, remains one of the standard treatments in this setting, having demonstrated improved OS compared to best supportive care (9). However, its clinical use is often limited due to frequent and severe hematological toxicities, along with a modest clinical benefit (10). The anthracycline-based regimen cyclophosphamide-adriamycin-vincristine (CAV) showed similar efficacy to topotecan in a phase III randomized trial (11). In 2020, lurbinectedin demonstrated an ORR of 22.2% in second-line treatment of platinum-resistant SCLC (12), but its combination with doxorubicin failed to improve OS compared to topotecan (13)