Biomarker Testing in Patients With Unresectable Advanced or Recurrent Non–Small Cell Lung Cancer

Abstract

ImportanceBiomarker testing for driver mutations is essential for selecting appropriate non–small cell lung cancer (NSCLC) treatment but is insufficient.ObjectiveTo investigate the status of biomarker testing and drug therapy for NSCLC in Japan for identifying problems in treatment.Design, Setting, and ParticipantsThe REVEAL cohort study included retrospective data collection and prospective follow-up from 29 institutions across Japan. Of 1500 patients diagnosed with advanced or recurrent NSCLC between January 1 and March 18, 2021, 1479 were eligible. Cases recognized at the wrong clinical stage (n = 12), diagnosed outside the study period (n = 6), not treated according to eligibility criteria before recurrence (n = 2), and with deficient consent acquisition procedure (n = 1) were excluded.Main Outcomes and MeasuresThe primary end point was the biomarker testing status. Treatment-related factors were examined.ResultsAmong the 1479 patients included in the analysis, the median age was 72 (range, 30-95) years; 1013 (68.5%) were men; 1161 (78.5%) had an Eastern Cooperative Oncology Group performance status 0 or 1; 1097 (74.2%) were current or past smokers; and 947 (64.0%) had adenocarcinoma. Biomarker status was confirmed in 1273 patients (86.1%). Multigene testing was performed in 705 cases (47.7%); single-gene testing, in 847 (57.3%); and both, in 279 (18.9%). Biomarker testing was performed for EGFR in 1245 cases (84.2%); ALK, in 1165 (78.8%); ROS1, in 1077 (72.8%); BRAF, in 803 (54.3%); and MET, in 805 (54.4%). Positivity rates among 898 adenocarcinoma cases included 305 (34.0%) for EGFR, 29 (3.2%) for ALK, 19 (2.1%) for ROS1, 11 (1.2%) for BRAF, and 14 (1.6%) for MET. Positivity rates among 375 nonadenocarcinoma cases were 14 (3.7%) for EGFR, 6 (1.6%) for ALK, 1 (0.3%) for ROS1, 3 (0.8%) for BRAF, and 8 (2.1%) for MET. Poor physical status, squamous cell carcinoma, and other comorbidities were associated with hampered multigene testing. Targeted therapy was received as first-line treatment by 263 of 278 cases (94.6%) positive for EGFR, 25 of 32 (78.1%) positive for ALK, 15 of 24 (62.5%) positive for ROS1, 9 of 12 (75.0%) positive for BRAF, and 12 of 19 (63.2%) positive for MET. Median overall survival of patients with positive findings for driver gene alteration and who received targeted therapy was 24.3 (95% CI, not reported) months; with positive findings for driver gene alteration and who did not receive targeted therapy, 15.2 (95% CI, 7.7 to not reported) months; and with negative findings for driver gene alteration, 11.0 (95% CI, 10.0-12.5) months. Multigene testing for nonadenocarcinomas and adenocarcinomas accounted for 705 (47.7%) of all NSCLC cases.Conclusions and RelevanceThese findings suggest that multigene testing has not been sufficiently implemented in Japan and should be considered prospectively, even in nonadenocarcinomas, to avoid missing rare driver gene alterations.

The Current Achievements of Multi-Gene Panel Tests in Clinical Settings for Patients with Non-Small-Cell Lung Cancer

“…Compared with an earlier period when the first multi-gene panel test, the ODxTT, was introduced into clinical practice in Japan [9,10,15], our results showed that the submission rate and the success rate of multi-gene panel tests have greatly improved. A recent report suggests that a multi-gene panel test performed prior to the initiation of systemic treatment can potentially enhance prognosis by detecting a wider range of driver oncogene alterations than multiple single-gene tests [5], and therefore the improvement in the submission rate and success rate of multi-gene panel tests is expected to contribute to a good prognosis for patients with NSCLC in clinical practice.…”

KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

“…Notably, BRAF mutations demonstrated a significantly higher frequency in patients with lung cancer with IPF, accounting for 6 of 35 cases (17.1%) [44], which is much higher than the known prevalence of 2-4% in the general lung cancer population [45,46]. As previously mentioned, a retrospective real-world study conducted in Japan [36] revealed that comorbidities, including IP, were associated with the absence of multiplex gene testing. Consequently, NSCLC patients with comorbid IP were not thoroughly investigated for multiple driver gene mutations, considering the underlying risk of drug-induced pneumonia.…”

“…Factors associated with the lack of multiplex gene testing were Eastern Cooperative Oncology Group Performance Status of 3 or 4 (odds ratio (OR): 0.47; 95% CI: 0.32-0.70; p < 0.005), comorbidities (OR: 0.54; 95% CI: 0.44-0.67; p < 0.005), and non-adenocarcinoma (OR: 0.70; 95% CI: 0.56-0.87; p < 0.005) in the multivariate model. Among patients with comorbidities, 10.5% had interstitial lung disease [36].…”

Errors in Figures and Supplement

“…In the Original Investigation titled “Biomarker Testing in Patients With Unresectable Advanced or Recurrent Non–Small Cell Lung Cancer,” 1 published December 15, 2023, the first 2 labels in the x-axis of Figure 1 were inadvertently transposed; the bars indicating multigene testing were inadvertently labeled as single gene testing in the color key of Figure 2; and 2 of the denominators in eTable 3 in Supplement 1 were incorrect (for surgical samples and others in the RNA analysis column). This article has been corrected.…”