Second-line therapy for disseminated small-cell lung cancer: optimal management remains to be defined - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles Translational Lung Cancer Research Year : 2020

Second-line therapy for disseminated small-cell lung cancer: optimal management remains to be defined


Lung cancer remains an important public health concern for both men and women, with significant morbidity and mortality. Small-cell lung cancer (SCLC) represents between 14% and 18% of all lung cancers. Two thirds are disseminated stages at diagnosis. Management of main SCLC is based on chemotherapy and platin-etoposide combination represents the therapeutic cornerstone for both localized and extensive disease (1). More recently, two pivotal phase 3 trials obtained promising results with the association of platinum-based chemotherapy and immunotherapy, either atezolizumab (2) or durvalumab (3). These chemotherapies or combination of immunotherapy and chemotherapies provide high objective response rates (ORR), but the majority of patients relapse. Second-line treatment for SCLC remains a challenge (4,5). In this second line setting, particular attention must be paid, in these patients who have a poor prognosis, to the quality of life but also to economic issues. In most randomized-controlled trials, ORR was observed in less than a quarter of patients and median overall survival (OS) range from 3.2 to 8.7 months. The factors associated with outcomes appeared to be associated with the type of firstline chemotherapy, the response to it (resistant, refractory or sensitive), treatment-free period and performance status at relapse (5). Few real-life studies have provided data on treatment efficacy in non-selected patients (6). Filling that gap, Zhao et al. (7) analyzed the results of 116 SCLC patients treated after a first line platin chemotherapy progression. The main chemotherapy regimens analyzed were irinotecan, topotecan, paclitaxel or docetaxel. Their respective progression-free survival (PFS) durations were comparable, at 3, 2.5, 2.7 or 1.7 months, but OS differed significantly for irinotecan, with 19 vs. 5, 5.6, or 6.1 months, respectively. In that analysis, the ORR to second-line therapy was positively associated with the response to first-line therapy (P=0.012). According to their multivariate analyses, treatmentfree interval <90 days, lactate dehydrogenase ≥225 U/L and neutrophil-to-lymphocyte ratio (NLR) ≥3.5 were independent risk factors for poor OS. That study had numerous limitations, particularly its retrospective design and monocenter setting. Even though it was a real-life study, the inclusion modalities did not allow us to know the number of patients who did not receive second-line therapy because of poor general conditions and, thus, the degree of selection of those analyzed. In real life setting, many SCLC patients do not receive second-line therapy. According to a German study (8), among the 432 consecutively included patients with advanced disease at diagnosis, only 50% of them received second-line therapy. In a Swedish mono-centric analyse (9) of 544 patients-408 metastatic and 136 with localized at diagnosis-only a quarter of the former received secondline therapy, with the rest given best supportive care (BSC). Median OS after starting second-line therapy was 10.2 and 4.4 months, respectively, for patients with sensitive or resistant SCLC. For patients with localized disease at diagnosis, only one-third of patients with received secondline treatment, which achieved a median PFS of 4.8 months and median OS of 8.2 months.


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hal-04143019 , version 1 (27-06-2023)



Christos Chouaïd, Nathalie Baize, Isabelle Monnet. Second-line therapy for disseminated small-cell lung cancer: optimal management remains to be defined. Translational Lung Cancer Research, 2020, 9 (5), pp.1732-1735. ⟨10.21037/tlcr-20-362⟩. ⟨hal-04143019⟩
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