Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50%

IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P < 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group.ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%

Rationale and design of phase II clinical trial of dual inhibition with ramucirumab and erlotinib in exon 19 deletion-positive treatment-naïve non-small cell lung cancer with high PD-L1 expression (SPIRAL-3D study)

Background: Osimertinib is a standard treatment option for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, osimertinib monotherapy yields poor clinical outcomes in some patients, necessitating the development of novel treatment strategies. In addition, several studies have suggested that high programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) for osimertinib monotherapy in patients with advanced NSCLC harboring EGFR mutations. Objective: To evaluate the clinical efficacy of erlotinib plus ramucirumab for EGFR exon 19 deletion-positive treatment-naïve NSCLC with high PD-L1 expression. Design: A single-arm, prospective, open-label, phase II study Methods and Analysis: Patients with treatment-naïve EGFR exon 19 deletion-positive NSCLC with high PD-L1 expression and a performance status of 0–2 will receive combination therapy with erlotinib plus ramucirumab until evidence of disease progression or development of unacceptable toxicity. High PD-L1 expression is defined as a tumor proportion score of 50% or higher, as determined by PD-L1 immunohistochemistry 22C3 pharmDx testing. The Kaplan–Meier method and the Brookmeyer and Crowley method with the arcsine square-root transformation will be used with PFS as the primary endpoint. The secondary endpoints include overall response rate, disease control rate, overall survival, and safety. A total of 25 patients will be enrolled. Ethics: The study has been approved by the Clinical Research Review Board, Kyoto Prefectural University of Medicine, Kyoto, Japan, and written informed consent will be obtained from all patients. Discussion: To the best of our knowledge, this is the first clinical trial to focus on PD-L1 expression in EGFR mutation-positive NSCLC. If the primary end point is met, combination therapy with erlotinib and ramucirumab could become a potential treatment option for this clinical population. Trial Registration: This trial was registered with the Japan Registry for Clinical Trials on 12 January 2023 (jRCTs 051220149)

Table_1_Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50%.docx

IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%.</p

Presentation_1_Prognostic impact of clinical factors for immune checkpoint inhibitor with or without chemotherapy in older patients with non-small cell lung cancer and PD-L1 TPS ≥ 50%.pptx

IntroductionThe proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO.MethodsWe retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching.ResultsOf the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P ConclusionsECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PD-L1 TPS ≥ 50%.</p