Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

Abstract

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death‐ligand 1 expression and blood‐based tumor‐mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood‐based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.

Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma

“…Besides, Qian et al found that blood-based mutation of GRM3 was associated with response to immunotherapy in NSCLC. 50 Combining these previous findings with our results, we considered that mutations in GRM3 may also play a key promotor in high TMB to increase the potential of response to ICIs in melanoma. However, the mechanism of how GRM3 takes impact on TMB is still unclear at present.…”

A meta-analysis comparing responses of Asian versus non-Asian cancer patients to PD-1 and PD-L1 inhibitor-based therapy

“…An ancillary analysis of individual patient data in the OAK and POPLAR studies suggested that baseline characteristics and genetic mutations may account for the differences of outcome for Asian and non-Asian patients receiving atezolizumab. 40 Ethnic differences in somatic mutations such as STK11, TP53 and EGFR were associated with treatment responses or survival. For example, the mutation rate of STK11 differs among Asian (1.6%) and non-Asian patients (12.3%), which was reported previously to affect efficacy of ICI.…”

EPHA5 mutation predicts the durable clinical benefit of immune checkpoint inhibitors in patients with lung adenocarcinoma

“…Previous studies have observed that EPHA5 is frequently mutated in several cancers, including NSCLC [25,42,43]. Mutations in the EPHA5 gene could impair NK cell-mediated cytotoxicity against cancer cells [25] and predict the overall prognosis of cancer patients [44]. In addition to the effects on gene mutations, changes in EPHA5 transcription levels also affect tumor progression (e.g., enhanced drug resistance, invasion and metastatic ability of cancer cells) [45][46][47].…”