Clinical characteristics of the patients
Total of 41 patients had been enrolled, and 39 (95.1%) patients were male. Median age was 69. Regarding smoking history, 40 (97.5%) patients were ever smoker. Among the 35 patients with survival data, 24 patients survived more than 6 months (68.6%). Twenty-six (63.4%) patients showed partial response (PR) as best response, while 9 (22.0%) patients showed stable disease (SD) as best response, and 4 (9.8%) patients showed progressive disease only. Thirty-nine (95.1%) patients underwent the combination treatment as first-line treatment, while 2 (4.9%) patients underwent as second-line treatment. Regarding median laboratory values at etoposide-carboplatin plus atezolizumab (EC-A) initiation, NLR showed 2.87, PLR was 163.5, derived NLR was 1.89, c-reactive protein (CRP) was 7.14mg/dl, and lactate dehydrogenase (LDH) was 351.0 units/L (Table 1).
Comparison of clinical characteristics between responders and non-responders
Among 39 patients with treatment response data, 13 patients were categorized as non-responders and 26 patients were categorized as responders. There was no statistically significant difference regarding sex and age. Six-month survival was 63.6% in the non-responder group and 77.3% in the responder group, with no statistically significant difference. There was 1 (7.7%) patient with brain metastasis in the non-responder group, while 6 (23.1%) patients in the responder group had brain metastasis at the time of treatment initiation. CRP and LDH were tended to be higher in the non-responder group (29.87 vs 5.25 and 510 vs 350.5, respectively), but there were no statistically significant differences. Also there were no significant differences in pulmonary function tests parameters (Table 2).
Treatment related AEs
Treatment related AEs were evaluated separately for induction (combination) and maintenance (atezolizumab) phases. Total of 40 patients were evaluated for AEs during the induction phase. For patients who completed the induction phases, 25 patients were evaluated for AEs during the maintenance phase. Among the 40 patients, 35 (87.5%) patients showed any grade AEs: 22 of 40 (53.7%) patients showed grade I-II AEs, and 26/40 (63.4%) patients showed grade III-IV AEs. Regarding grade I-II AEs, thrombocytopenia (n=9, 22.5%), neutropenia (n=7, 17.5%), anemia (n=7, 17.5%), and acute kidney injury (n=4, 10.0%) were the most frequent AEs. Among grade III-IV AEs, neutropenia (n=18, 45.0%), neutropenic fever (n=5, 12.5%), anemia (n=4, 10.0%), and nausea (n=3, 7.5%) were the most frequent AEs.
Among the 25 patients evaluated for AEs occurred in the maintenance phase, 9 (36.0%) patients showed any grade AEs: 6 (24.0%) patients showed grade I-II AEs and 4 (16.0%) patients showed grade III-IV AEs. Regarding grade I-II AEs, there was one case per each AE (hyperthyroidism, hypothyroidism, colitis, adrenal insufficiency, AKI and thrombocytopenia). There were four documented cases of grade III-IV AEs: pancreatitis, hepatitis, pneumonitis, and AKI (Table 3).
Analysis for association with OS and PFS
Among the patients who have valid survival data, cox regression analysis for OS was performed. Age, sex, smoking history, Eastern Cooperative Oncology Group (ECOG) score, primary mass size, number of metastatic sites, NLR, PLR, dNLR, LDH, CRP, FEV1 (%) and FVC (%) were entered for univariate analysis. In the multivariate analysis, age, sex, number of metastatic sites, LDH, CRP and FVC (%) were entered. LDH (HR=1.001, 95% CI 1.000-1.003, P=0.036), CRP (HR=1.036, 95% CI 1.014-1.059, P=0.001), and FVC (%) (HR=1.135, 95% CI 1.012-1.273, P=0.031) were statistically significant factors that showed association with OS (Table 4).
Cox-regression analysis for PFS was performed. In the univariate analysis, sex, smoking history, number of metastatic sites, and LDH showed p-value less than 0.1. In the multivariate analysis, sex (HR 16.892, 95% CI 1.348-211.7, P=0.028) and LDH (HR 1.001, 95% CI 1.000-1.002, P=0.003) were statistically significant factors that showed association with PFS (Table 5).