Outcomes of Chemoimmunotherapy Among Patients With Extensive-Stage Small Cell Lung Cancer According to Potential Clinical Trial Eligibility

Abstract

ImportanceChemoimmunotherapy is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). However, whether findings from pivotal trials can be extrapolated to the clinical practice setting remains unclear.ObjectiveTo compare treatment outcome gaps following first-line chemoimmunotherapy for patients with ES-SCLC between those who met and did not meet the eligibility criteria used in previous clinical trials.Design, Setting, and ParticipantsA prospective cohort study was conducted from September 1, 2019, to September 30, 2020, at 32 hospitals in Japan, with at least 12 months of follow-up. Participants included consecutive patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as first-line therapy.ExposuresPatients who met eligibility criteria for pivotal phase 3 clinical trials were considered trial-eligible.Main Outcomes and MeasuresThe primary outcome was 6-month progression-free survival. The secondary outcomes were differences in progression-free survival, overall survival, and safety according to whether key clinical trial eligibility criteria were met.ResultsA total of 207 patients were analyzed (median age, 72 years; range, 46-87 years; 170 [82%] were male). Sixty-four patients (31%) were older adults (age ≥75 years), and most (184 [89%]) had an Eastern Cooperative Oncology Group performance status of 0 or 1. There were 132 (64%) trial-eligible patients. The 6-month progression-free survival rate for all patients was 38.8% (95% CI, 32.4%-45.7%). The median progression-free survival was 5.1 months in trial-eligible patients and 4.7 months in trial-ineligible patients (hazard ratio, 0.72; 95% CI, 0.53-0.97; P = .03). The proportion of patients who achieved disease control was 93% (118 of 127) in trial-eligible patients and 77% (55 of 71) in trial-ineligible patients (P = .002). The median overall survival was 15.8 months in trial-eligible patients and 13.1 months in trial-ineligible patients (hazard ratio, 0.73; 95% CI, 0.51-1.07; P = .10). The rate of severe adverse events was numerically higher among trial-ineligible patients than among trial-eligible patients (39% vs 27%; P = .07).Conclusions and RelevanceIn this cohort study, the overall treatment outcome was comparable to that reported in pivotal clinical trials. However, treatment outcomes after chemoimmunotherapy might differ between trial-eligible and trial-ineligible patients. These findings suggest that trial-eligibility criteria may be useful in clinical practice, and further studies using data from clinical practice settings are required to inform regulatory approval and clinical decision-making.

Machine learning analysis of pathological images to predict 1-year progression-free survival of immunotherapy in patients with small-cell lung cancer

“…The overall study result was already published elsewhere. 19 The patient selection process is shown in online supplemental figure 2 , while the baseline clinical characteristics are shown in table 1 . The patients’ median age was 78 years.…”

“…This 32-centered, prospective, and hospital-based cohort study was a biomarker analysis of the APOLLO study, using patients with ES-SCLC who received carboplatin and etoposide with atezolizumab as first-line treatment in Japan between September 2019 and September 2020. 19 In addition to the eligibility criteria in the APOLLO study, patients in whom adequate biopsy specimens were obtained before initiating the first-line treatment were included. We only used biopsy samples from the lungs to accurately evaluate the TIME status.…”

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

“…Fujimoto et al. conducted a prospective observational study utilizing real‐world data of ES‐SCLC with ICI to chemotherapy in Japan 27 . Their findings indicated that patients not eligible for inclusion in clinical trials experienced a higher frequency of Grade 3 or higher adverse events 27 .…”

“…Fujimoto et al conducted a prospective observational study utilizing real-world data of ES-SCLC with ICI to chemotherapy in Japan. 27 Their findings indicated that patients not eligible for inclusion in clinical trials experienced a higher frequency of Grade 3 or higher adverse events. 27 Therefore, we attribute the higher occurrence of Grade 3 or higher adverse events in our data to the inclusion of real-world patients, encompassing demographics not typically represented in clinical trials, such as elderly patients and those with poor performance status.…”

Treatment patterns and clinical outcomes in 157 patients with extensive-stage small cell lung cancer: real-world evidence from a single-center retrospective study

“…Fujimoto et al. ( 22 ) thought that trial-ineligible patients may be the reason caused the difference between the clinical trial and reality.…”