Real-world comparison of immune checkpoint inhibitors in non-small cell lung cancer following platinum-based chemotherapy

Abstract

Purpose Immunotherapy is a relatively new treatment modality for advanced non-small cell lung cancer following platinum-based chemotherapy. Nivolumab, pembrolizumab, and atezolizumab demonstrated superior outcomes and improved tolerability compared to standard treatment in randomized controlled trials; however, these studies vary significantly in inclusion criteria and study design. To our knowledge, the efficacy and safety of nivolumab and atezolizumab following platinum-based chemotherapy have not been directly compared to one another in a real-world clinic setting. Methods We retrospectively compared immunotherapy response rates and toxicity in patients with stage IV or recurrent non-small cell lung cancer following progression during or after platinum-based chemotherapy. Results Among 124 eligible patients, the objective response rate was 14.8% in the nivolumab group (n = 81) vs. 13.9% in the atezolizumab group (n = 43) (p = 0.897). Median overall survival was 8.4 months with nivolumab (95% confidence interval (CI), 6.3 to 11.2) vs. 6.5 months with atezolizumab (95% CI, 4.7 to not reached). Median progression free survival was 2.2 months (95% CI, 1.7 to 2.8) and 2.0 months (95% CI, 1.8 to 2.7) in the nivolumab and atezolizumab groups, respectively. Treatment-related adverse events occurred in 70.4% of patients in the nivolumab group and 65.1% in the atezolizumab group. Conclusions There was no statistically significant difference in efficacy outcomes in patients with non-small cell lung cancer who received atezolizumab or nivolumab after progression during or after platinum-based chemotherapy. Response rates in this study were numerically lower than response rates observed in the landmark randomized controlled trials leading to approval of immunotherapy in this setting. Rates of treatment-related adverse events were similar between groups.

Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer

“…The vast majority of the real-world data about immunotherapy in lung cancer describes the activity, in terms of objective response rate (ORR), efficacy (in terms of overall survival, OS, and progression free survival, PFS) and the safety profile of the most common ICIs used in clinical practice (Table 1). Studies on pretreated NSCLC patients were all retrospective and showed outcomes comparable with those reported in the pivotal RCTs, with median PFS and median OS ranging from 1.8 to 4.9 months and from 7.9 to 14.6 months, respectively [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Only one study showed a remarkable outcome for patients treated with nivolumab, with a median PFS exceeding 8 months and a median OS of over 15 months; however, this may be due to the small population (n = 11) considered for analysis [23].…”

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

“…Atezolizumab and nivolumab, PD-L1 and PD-1 antibodies, respectively, are proven to be effective and safe in clinical trials [ 3 , 4 , 6 ] and after approval by authorities in real-world studies ( Table 1 ) [ 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, there is no head-to-head clinical trial that compares the results of each drug, and to our knowledge, there are only two real-world studies that have compared outcomes between the two ICIs [ 11 , 12 ]. However, they did not perform a head-to-head subgroup analysis between the two ICIs.…”

“…This contrast in the real-world outcomes (PFS, OS and ORR) is due to several factors, such as the inclusion of a very heterogeneous population between studies that include patients who are generally excluded from clinical trials, including elderly patients, heavily pretreated, patients with an ECOG score greater than or equal to 2, CNS metastasis and/or with numerous comorbidities. For example, poor survival outcomes have been obtained in studies that include a high number of patients with negative prognostic factors such as ECOG ≥ 2 or metastases in the CNS [ 12 , 22 , 23 , 24 ]. In our cohort, 15.2% of patients had ECOG ≥ 2, and 16.5% had CNS metastases at baseline, similar to other real-world studies [ 9 , 16 , 17 ] and higher than those included in the pivotal studies, 1.5%, 0% and 0% for ECOG ≥ 2 and 6.6%, 11.6% and 10% for CNS metastases in Checkmate017, Checkmate057 and OAK, respectively.…”

“…To our knowledge, only two studies compared them. Ramagopalan et al [ 11 ] studied them in a large cohort that compared the effectiveness (OS), and Weis et al [ 12 ] compared survival, response and toxicity, concluding in both cases that there was no statistically significant difference between the two treatments. With this aim, the main objective of this work is to characterize and compare the results (survival, response and safety) between nivolumab and atezolizumab in pretreated (second- and third-line treatment) patients with advanced NSCLC.…”

Treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer initiating first-line treatment in the US community oncology setting: a real-world retrospective observational study

“…However, few studies have examined the real-world treatment patterns and clinical outcomes of these therapies. These studies have mostly included patients with previously treated advanced NSCLC, lacked comparisons between treatments, and/or limited the patient population to those with PD-L1 expression (Khozin et al 2018 ; Molife et al 2019 ; Nadler et al 2018 ; Schwartzberg et al 2019 ; Velcheti et al 2019 ; Weis et al 2019 ). Further research on IO use in patients with advanced NSCLC treated in the community oncology setting is needed, as there may be differences in real-world clinical outcomes compared with clinical trial outcomes due to underlying variation in patient populations and methodology (Khozin et al 2019a ).…”