Real-World Evidence Supports Chemoimmunotherapy in ES-SCLC With Poor PS

A single-institution retrospective analysis provides insight into treatment strategies for patients with extensive-stage small cell lung cancer (ES-SCLC) who present with poor functional status, a population often excluded from pivotal clinical trials and underrepresented in real-world evidence. The findings, published in Cancer Medicine, suggest that incorporation of immune checkpoint inhibitors (ICIs) into platinum-doublet regimens improved overall survival for SCLC patients with ECOG PS 2 to 3, but conferred no survival benefit in those with ECOG 0 to 1.¹

The study reviewed outcomes of 74 patients with ES-SCLC treated between 2019 and 2022 at Saitama Medical Center in Japan. Patients were stratified by performance status and whether they received a platinum-doublet chemotherapy alone or in combination with an ICI—specifically, atezolizumab or durvalumab. Thirty-two patients received ICI-based therapy, while 42 received chemotherapy alone. The median age was lower in the ICI group compared to the non-ICI group (70 years vs 75 years, respectively; P = .0065); however, the distributions of sex, clinical stage, and performance status were not statistically different.

Across the entire cohort, the median OS was 327 days, with an overall objective response rate (ORR) of 67.6%. The addition of ICI improved OS across the entire cohort compared to the chemotherapy-alone group (448 days vs. 291 days), but this difference was not statistically significant (P = .131). The addition of ICIs improved the ORR across all patients, with 84.4% in the ICI arm versus 54.8% in the chemotherapy-alone arm (P = .0144). “Among multiple variables, including age, ECOG-PS, and the addition of ICIs, logistic regression analysis identified the addition of ICIs as the sole factor associated with better ORR,” the authors explained.

When stratified by performance status, patients with ECOG-PS 2 to 3 who received additional therapy with ICIs were found to have a significant survival benefit with a median OS of 448 days with ICI versus just 169 days with chemotherapy alone (P = .00661). In contrast, there was no observed OS benefit in patients with ECOG-PS 0 to 1, where ORR was modestly higher with ICIs (76.5% vs 56.5%), but OS outcomes were similar between the ICI (406 days) and chemotherapy-alone groups (379 days; P = .911).

Treatment adverse reactions were generally manageable, even in patients with poor ECOG-PS. Severe hematologic toxicities (grade ≥3) were more common in patients receiving chemotherapy alone. Neutropenia occurred in 85.7% of patients in the chemotherapy alone group, compared with 62.5% in the ICI group, while severe anemia occurred in 23.8% of patients in the chemotherapy alone group, compared with 3.1% with ICIs. Nine patients discontinued immunotherapy due to immune-related adverse events, including pneumonitis, hypopituitarism, encephalitis, and diarrhea.

These findings indicate that the addition of atezolizumab or durvalumab to platinum-doublet chemotherapy improves the ORR and results in a better prognosis for patients with ES-SCLC and ECOG-PS 2 to 3, and “highlight a potential treatment opportunity for a patient population often underrepresented in clinical trials.”

“The absence of a significant survival benefit in the ECOG PS 0–1 subgroup appears to be inconsistent with the findings of pivotal studies such as the IMpower133 trial and the CASPIAN trial,” the authors note.^2,3

However, the applicability of these regimens to patients with poorer performance status has remained largely unknown. Investigators suggest that the unexpectedly long median OS in the chemotherapy-only cohort with ECOG-PS 0-1 (379 days) may have limited the ability to detect incremental benefit from immunotherapy in this subgroup.¹ By contrast, tumor shrinkage with ICIs appeared to translate into clinically meaningful benefit in patients with ECOG-PS 2 to 3, for whom baseline prognosis is typically poor.

While acknowledging the limitations inherent in a single-institution retrospective study, including its observational nature and potential for patient imbalances, the results provide valuable real-world evidence for future clinical decision-making.

References

1. Sakai K, Ishii S, Yokosuka S, et al. Efficacy of immune checkpoint inhibitors in combination with platinum-based doublet chemotherapy for extensive-stage small-cell lung cancer patients with Eastern Cooperative Oncology Group-Performance Status 2-3: A single-institution retrospective study. Cancer Med. 2025;14(17):e71136. doi:10.1002/cam4.71136

2. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220-2229. doi:10.1056/NEJMoa1809064

3. Paz-Ares L, Dvorkin M, Chen Y, et al.; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi:10.1016/S0140-6736(19)32222-6