Comparison of ICI plus chemotherapy or ipilimumab plus nivolumab based therapy for patients with NSCLC with TPS (1-49%): TOPGAN2023-01.

8550 Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.