Efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in real world elderly patients with small cell lung cancer / 中华老年医学杂志

ABSTRACT

Objective:To investigate the efficacy and adverse effects of first-line immunotherapy combined with chemotherapy in elderly patients with small cell lung cancer(SCLC)in population of real world.Methods:A total of 148 elderly SCLC patients(age ≥65 years old)underwent pathological diagnosis were retrospectively analyzed from January 2013 to June 2023.103 patients received chemotherapy(chemotherapy group), and 45 patients received immunotherapy combined with chemotherapy(combination group). Patients were divided into senior group(≥75 years old)and younger group(<75 years old)by age.To compare the efficacy of different regimens in first-line treatment, the expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and Log-rank test were performed.Cox regression was used in prognostic analysis.Results:The overall response rate(ORR)of the first-line combination group in elderly SCLC patients was 79.1%(34/43), which was higher than that of the chemotherapy group 63.2%(60/95), but the difference did not reach statistical significance( χ2=3.451, P=0.063). ORR was significantly higher in the combination group than in the chemotherapy group for patients in the ≥75-year-old group, 87.5%(7/8) vs.48.6%(17/35), respectively( χ2=4.001, P=0.045). The difference in median progression-free survival time(mPFS)in the combination group compared with the chemotherapy group was not statistically significant in the overall patients(5.43 months vs.6.07 months, P=0.660). The combination group prolonged patients' median overall survival time(mOS)compared with the chemotherapy group, but the difference did not reach statistical significance(13.63 months vs.11.97 months, P=0.205). In patients ≥75 years old, mPFS was lower in the combination group than in the chemotherapy group(2.97 months vs.6.47 months), but mOS was prolonged compared with that in the chemotherapy group(13.50 months vs.11.40 months), and none of the differences reached statistical significance(both P>0.05). The differences in mPFS and mOS between the combination group and the chemotherapy group were not statistically significant in patients <75 years old(both P>0.05). In elderly patients with severe comorbidities, mPFS and mOS were lower in the combination group than in the chemotherapy group(5.40 months vs.7.30 months and 10.70 months vs.12.27 months, both P>0.05). In patients without severe comorbidities, the difference in mPFS between the combination group and the chemotherapy group was not statistically significant( P>0.05), but the mOS was significantly longer in the combination group(20.57 months vs.11.57 months, P=0.054). Elderly SCLC patients had a positive PD-L1 tumor cell positive proportion score(TPS)rate(≥1%)of 23.5%(4/17)and a high TMB(≥9 mut/Mb)expression rate of 69.0%(11/16). The overall incidence of immune-related adverse reactions was 71.0%(32/45), grade 3 or higher 33.3%(15/45), and the most common grade 3 adverse reactions were rash, immune-related pneumonia and malaise. Conclusions:First-line immune-combination chemotherapy improves ORR and mOS over chemotherapy in elderly SCLC patients; mOS benefit of immune-combination chemotherapy is more pronounced in patients ≥75 years of age without severe comorbidities, low PD-L1 positivity and high TMB expression are present in elderly SCLC patients, and immune-related adverse effects are generally manageable in elderly patients.