Comparison of real-world data (RWD) analysis on efficacy and post-progression outcomes with pembrolizumab plus chemo vs chemo alone in metastatic non-squamous non-small cell lung cancer with PD-L1 < 50%

Abstract

BackgroundFollowing the introduction of immunotherapy (IO) in the first-line (1L) treatment in patients with non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutations, increasing real-world data depict how difficult it is to replicate data from clinical trials to clinical practice, with high rates of early treatment failure. In the context of chemo-IO, our study aims to compare platinum-pemetrexed-pembrolizumab combination to platinum-doublet alone in patients with low PD-L1 (&amp;lt;50%).MethodsWe retrospectively collected medical records from patients with stage IV non-squamous NSCLC with PD-L1&amp;lt;50%, consecutively treated at our Centre from 2016 to 2021. Patients were grouped according to 1L treatment received: chemo-IO (group A) or platinum-doublet (group B). Survival outcomes were analyzed and compared among the two groups.ResultsOverall, 105 patients were included: 49 in group A and 56 in group B. At data cut-off, median follow-up was 12.4 and 34.8 months, with 32/49 and 52/56 events for progression-free survival (PFS) and 21/49 and 29/56 events for overall survival (OS), respectively. No difference in PFS was observed between group B and group A (6.6 versus 8 months, HR 1.12, 95%CI 0.57-1.40). Patients receiving 1L platinum-doublet had significantly longer OS compared to those receiving chemo-IO (median OS 23.8 vs 14.9 months, HR 0.47, 95% CI 1.15- 3.98, p=0.01). 12 month-OS was 58% (95% CI 44-76%) in group A and 78% (95% CI 68-91%) in group B (p=0.040). Subgroup analysis identified KRAS G12C mutation as potentially affecting PFS in patients receiving chemo-IO (HR 0.29, 95% CI 0-10-0.91). The OS benefit of platinum-doublet was consistent across subgroups, with particular benefit in female sex, liver or pleural metastases, PD-L1 negative. Overall, only 46.9% of patients with progression received subsequent treatment in group A (15/32), compared to 86.5% in group B (45/52, all receiving 2L IO), with no difference in PFS to 2L (group A 3.7months, group B 4.1months, p=0.3).ConclusionsDespite small study population and differential follow-up, our study demonstrates that sequential use of 1L platinum-doublet and 2L IO is not inferior to 1L chemo-IO in non-squamous NSCLC with PD-L1&amp;lt;50%. In addition, we identified subgroups who might benefit differentially from the two approaches.

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice

“…In our analysis, age was not significant, while performance status, higher disease burden, and disease progression had a negative impact on OS. Other authors have confirmed those observations and highlighted the impact of performance status and a higher probability of premature termination of treatment in real life than in clinical trials (24)(25)(26)(27). Table 5 includes a summary of real-world studies in NSCLC patients with tumours showing negative PD-L1 expression.…”

First-Line Chemoimmunotherapy versus Sequential Platinum-Based Chemotherapy Followed by Immunotherapy in Patients with Non-Small Cell Lung Cancer with ≤49% Programmed Death-Ligand 1 Expression: A Real-World Multicenter Retrospective Study

“…Thus, patients with a relatively favorable prognosis may have been included in the SEQ group compared to those in the CIT group. In previous reports, approximately 8% of the patients failed to switch to second-line treatment after first-line treatment, suggesting that the SEQ strategy for these patients would jeopardize the opportunity for ICI treatment [26]. Third, the difference in the follow-up period and subsequent treatment options may have affected the outcomes since CIT was approved approximately two years later than second-line ICI monotherapy.…”

“…Although several reports have compared the prognostic value of CIT and pembrolizumab monotherapy [22][23][24][25], reports comparing CIT and SEQ are scarce, with only one report on non-squamous NSCLC with a small sample size showing the non-inferiority of sequential treatment over CIT [26]. Thus, whether SEQ in patients with NSCLC with ≤49% PD-L1 expression is comparable to that of CIT is unclear.…”

Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non–Small Cell Lung Cancer

“…Observational data from clinical practice for pembrolizumab plus chemotherapy for older adult patients in China indicated that grade 3 and higher pneumonitis occurred in 9%, and AEs leading to discontinuation registered 26% . Another study conducted in Italy reported grade 3 and higher pneumonitis occurring in 10.2% of patients receiving a combination of pembrolizumab, platinum, and pemetrexed with a median age of 68 years . Furthermore, Morimoto et al reported that the incidence of grade 3 and higher pneumonitis reached 16.0% in patients 75 years and older who received pembrolizumab with platinum and pemetrexed in Japan.…”

“…19 Another study conducted in Italy reported grade 3 and higher pneumonitis occurring in 10.2% of patients receiving a combination of pembrolizumab, platinum, and pemetrexed with a median age of 68 years. 31 Furthermore, Morimoto et al 32 reported that the incidence of grade 3 and higher pneumonitis reached 16.0% in patients 75 years and older who received pembrolizumab with platinum and pemetrexed in Japan. Considering these results, ICI-chemotherapy resulted in an increased frequency of severe pneumonitis relative to ICI alone, especially in older adults.…”