Predictors of outcomes in advanced non-small cell lung cancer treated with pembrolizumab maintenance

Abstract

Background: Real-world first-line maintenance (1LM) treatment data are limited for advanced/metastatic non-small cell lung cancer (a/mNSCLC).

Materials and methods: In this electronic health record-derived, deidentified database study, eligible patients (≥18 years; diagnosed with stage III/IV non-small cell lung cancer [June 1, 2017-September 30, 2021]) initiated pembrolizumab-based 1LM after 4-6 cycles of first-line (1L) platinum-based chemotherapy-pembrolizumab ± pemetrexed. Study outcomes were real-world time to next treatment or death (rwTTNTD), overall survival (rwOS), and predictors of outcomes.

Results: Of 1944 patients analyzed (median follow-up, 12.2 months), 51.9% received 1LM pembrolizumab-pemetrexed and 48.1% pembrolizumab monotherapy. Median rwTTNTD and rwOS were 9.2 (95% CI: 8.5-9.8) and 18.7 (95% CI: 17.7-20.3) months, respectively. In multivariable analyses, factors significantly associated with shorter rwTTNTD included 5%-<10% (hazard ratio [HR], 1.34; 95% CI: 1.17-1.54) or ≥10% (HR, 1.69; 95% CI: 1.42-2.01) weight loss during 1L versus 0% or <5% weight loss. Programmed death-ligand 1 (PD-L1) expression 1%-49% (HR, 0.81; 95% CI: 0.71-0.93) or ≥50% (HR, 0.55; 95% CI: 0.47-0.64) and female sex (HR, 0.85; 95% CI: 0.75-0.95) were significantly associated with longer rwTTNTD. These variables were also significantly associated with shorter (weight loss 5%-<10%: HR, 1.52; 95% CI: 1.30-1.77; ≥10% HR, 2.06; 95% CI: 1.71-2.48) and longer rwOS (PD-L1 expression: 1%-49% HR, 0.84; 95% CI: 0.72-0.98; ≥ 50% HR, 0.57; 95% CI: 0.48-0.68; female sex: HR, 0.81; 95% CI: 0.71-0.92).

Conclusions: Predictors of real-world clinical outcomes included 1L treatment, weight loss, PD-L1 status, and sex. Poor outcomes persisted despite immunotherapy-based 1LM availability, revealing an unmet need in this population.

Keywords: electronic health records; non-small cell lung cancer; pembrolizumab; pemetrexed; retrospective studies.

Figure 1.

Study population. Abbreviations: 1L, first-line; 1LM, first-line maintenance; a/m, advanced/metastatic; NSCLC, non-small cell lung cancer; PARP, poly(ADP-ribose) polymerase. ^aDefined as the date on which pembrolizumab-based 1LM therapy was first administered.

Figure 2.

Treatment in the overall cohort. The 1L treatment regimen for patients in the overall cohort (n = 1944) (A), the proportion of patients who received pembrolizumab or pembrolizumab + pemetrexed as 1LM based on 1L treatment regimen (B), the 2L treatment regimen for patients who received pembrolizumab as 1LM (n = 935) (C), and 2L treatment regimen for patients who received pembrolizumab + pemetrexed as 1LM (n = 1009) (D). Abbreviations: 1L, first-line; 1LM, first-line maintenance; 2L, second-line. ^aThis group includes 1468 patients (75.5%) treated with carboplatin, pembrolizumab, and pemetrexed, and 27 patients (1.4%) treated with abiraterone, carboplatin, pembrolizumab, and pemetrexed. ^bOther regimens include regimens not defined in previous drug classes, such as sotorasib, capmatinib, and gemcitabine/vinorelbine.

Figure 3.

(A) rwTTNTD and (B) rwOS by histology. Abbreviations: 1LM, first-line maintenance; NOS, not otherwise specified; NSCLC, non-small cell lung cancer; rwOS, real-world overall survival; rwTTNTD, real-world time to next treatment or death.

Figure 4.

Predictors of (A) rwTTNTD and (B) rwOS in multivariable analyses. For rwTTNTD (A), index year (2017, 2019, 2020, and 2021 vs. 2018), index age (65-79 years and ≥ 80 years vs. 18-64 years), ethnicity (Hispanic/Latino vs not Hispanic/Latino), region (Northeast, Midwest, West, and unknown vs. South or other), histology (NSCLC NOS and squamous cell carcinoma vs. nonsquamous cell carcinoma), smoking history (history of smoking vs. no history of smoking), hemoglobin (abnormal^b vs. normal/unknown), aspartate aminotransferase (abnormal vs. normal/unknown), calcium (high vs. normal/unknown), monocytes (low and unknown vs. normal), alanine aminotransferase (low and high vs. normal/unknown), creatinine (high vs. normal/unknown), and NLR (unknown vs. low/≤median) were also evaluated and shown to be nonsignificant. For rwOS (B), index year (2017, 2019, 2020, and 2021 vs. 2018), index age (65-79 years and ≥80 years vs. 18-64 years), region (Northeast, West, and unknown vs. South or other), ECOG PS (unknown vs. 0-1), histology (NSCLC NOS and squamous cell carcinoma vs. nonsquamous cell carcinoma), cardiovascular disease (yes vs. no), calcium (low and high vs. normal/unknown), monocytes (low and unknown vs. normal), alanine aminotransferase (low and high vs. normal/unknown), creatinine (high vs. normal/unknown), NLR (high/>median vs. low/≤median), and PLR (unknown vs. low/≤median) were also evaluated and shown to be nonsignificant. Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; NLR, neutrophil-to-lymphocyte ratio; NOS, not otherwise specified; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; PLR, platelet-to-lymphocyte ratio; rwOS, real-world overall survival; rwTTNTD, real-world time to next treatment or death. ^aConsists of clinically low albumin levels (n = 262) versus high albumin levels (n = 1). ^bConsists of clinically low hemoglobin levels (n = 1721) versus high hemoglobin levels (n = 2).