Continuous Second-Line Immunotherapy May Benefit Pretreated Lung Cancer

Patients with driver gene–negative non–small cell lung cancer who received immunotherapy beyond progression experienced better survival outcomes.

Continuous second-line immunotherapy beyond progression following initial treatment with immune checkpoint inhibitor (ICI) therapy may provide benefit for patients with driver gene–negative non–small cell lung cancer (NSCLC) or SCLC, according to findings from a retrospective study published in Cancer Immunology, Immunotherapy.

Efficacy data revealed that in patients with driver gene–negative NSCLC and SCLC who received immunotherapy beyond progression (IBP) after ICI therapy, the median progression-free survival (PFS) was 4.7 months and 3.9 months, respectively. In those who received non-immunotherapy beyond progression (NIBP), the median PFS was 1.3 months (HR, 0.29; P <.01) and 2.1 months (HR, 0.38; 95% CI, 0.16-0.87; P = .02), respectively. Additionally, the median overall survival (OS) was 11.03 months and 9.28 months in the respective IBP patient populations vs 2.63 months (HR, 0.13; P <.001) and 2.27 months (HR, 0.23; 95% CI, 0.08-1.77; P <.01) in the respective NIBP populations.

Furthermore, in patients with NSCLC, no significant difference in objective response rate (ORR) was observed in the IBP group vs the NIBP group; 35.9% vs 30.3% (P = .57). However, a significant difference in disease control rate (DCR) was observed between both groups; 71.8% vs 54.5% (P = .078). In those with SCLC, differences in ORR and DCR between IBP and NIBP groups were nonsignificant. The ORR was 38.7% vs 12.5% in respective groups (P = .161), and the DCR was 80.6% vs 62.5% (P = .277).

Subgroup analysis showed an enhanced median PFS and OS benefit in patients with driver gene-negative NSCLC. The median PFS in this patient subgroup was 4.77 months with IBP vs. 1.17 months with NIBP (HR: 0.31, 95% CI, 0.15–0.64, P <.001) and the median OS was 11.93 months vs. 2.63 months (HR: 0.10, 95% CI, 0.01–0.74, P <.01).

“Continuous immunotherapy as a second-line treatment following disease progression during initial immunotherapy may improve clinical outcomes in patients with driver gene–negative NSCLC and SCLC,” Jing Cheng, of the department of Respiratory and Critical Care Medicine at the Nanjing Jingling Hospital of Nanjing University in China, wrote in the publication with study coinvestigators.¹ “In [patients with] advanced NSCLC with driver gene–negative status who have achieved a favorable response to prior treatment, continuation of immunotherapy beyond progression may be associated with improved survival. Larger prospective clinical trials are necessary to further validate these findings.”

The retrospective study enrolled adult patients 18 years and older with advanced or surgically resected stage III to IV or postoperative recurrent NSCLC (n = 111) or SCLC (n = 39) following the receipt of first-line ICI-based therapy from January 2020 to December 2023. Patients additionally had an ECOG performance status score of 0 to 2. Patients were classified by subsequent second-line therapeutic regimen received––either IBP or NIBP.

Patients in the IBP group accounted for 70.3% of those with NSCLC and 79.5% of those with SCLC. Furthermore, the majority of patients with NIBP in both populations received immunotherapy plus chemotherapy with or without anti-angiogenic therapy as a second-line regimen.

The trial end points included best clinical response, ORR, DCR, median PFS, median OS, and treatment-related adverse effects (TRAEs) per CTCAE v 5.0 guidelines.

Safety data revealed that among all-comers, 85.3% of patients with either NSCLC or SCLC experienced TRAEs during second-line treatment. Furthermore, in patients with NSCLC, 9.0% of the IBP group vs 18.2% of the NIBP group experienced grade 3/4 AEs (P =.17); in those with SCLC, grade 3/4 toxicity rates in respective groups were 9.7% vs 37.5% (P =.05). No grade 5 TRAEs were observed.

Reference

Cheng J, Kang W, Chen Y, Pan L, Han H, Lv T. Continuous immunotherapy beyond disease progression in patients with advanced non-small cell and small cell lung cancer. Cancer Immunol Immunother. 2025;74:124. doi:10.1007/s00262-025-03958-9