Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In a randomized, open-label, phase III NEJ009 study, gefitinib plus chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with gefitinib-alone in patients with untreated non–small-cell lung cancer harboring mutations in epidermal growth factor receptor. Herein, we report the updated survival outcome and long-term tolerability. Patients were randomly assigned to gefitinib (gefitinib 250 mg orally, once daily) and gefitinib combined with carboplatin plus pemetrexed (GCP in a 3-week cycle for six cycles followed by concurrent gefitinib and pemetrexed maintenance) groups. At the data cutoff (May 22, 2020), GCP demonstrated significantly better PFS2 (hazard ratio, 0.77; 95% CI, 0.62 to 0.97; P = .027) than gefitinib. However, the updated median OS was 38.5 months (95% CI, 31.1 to 47.1) and 49.0 months (95% CI, 41.8 to 56.7) in the gefitinib and GCP groups, respectively (hazard ratio, 0.82; 95% CI, 0.64 to 1.06; P = .127). The OS in both groups was similar for the overall patient population. No severe adverse events occurred since the first report. This updated analysis revealed that the GCP regimen improved PFS and PFS2 with an acceptable safety profile compared with gefitinib-alone. GCP is more efficient than gefitinib monotherapy as a first-line treatment for non–small-cell lung cancer with epidermal growth factor receptor mutations.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease implicated as an independent risk factor for lung cancer. However, optimal treatment for advanced lung cancer with IPF remains to be established. We performed a randomised phase 3 trial (J-SONIC) to assess the efficacy and safety of nintedanib plus chemotherapy (experimental arm) compared with chemotherapy alone (standard-of-care arm) for advanced nonsmall cell lung cancer (NSCLC) with IPF.Methods: Chemotherapy-naïve advanced NSCLC patients with IPF were allocated to receive carboplatin (area under the curve of 6 on day 1) plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) (100 mg·m⁻²on days 1, 8 and 15) every 3 weeks with or without nintedanib (150 mg twice daily, daily). The primary end-point was exacerbation-free survival (EFS).Results: Between May 2017 and February 2020, 243 patients were enrolled. Median EFS was 14.6 months in the nintedanib plus chemotherapy group and 11.8 months in the chemotherapy group (hazard ratio (HR) 0.89, 90% CI 0.67–1.17; p=0.24), whereas median progression-free survival was 6.2 and 5.5 months, respectively (HR 0.68, 95% CI 0.50–0.92). Overall survival was improved by nintedanib in patients with nonsquamous histology (HR 0.61, 95% CI 0.40–0.93) and in those at GAP (gender–age–physiology) stage I (HR 0.61, 95% CI 0.38–0.98). Seven (2.9%) out of 240 patients experienced acute exacerbation during study treatment.Conclusions: The primary end-point of the study was not met. However, carboplatin plus nab-paclitaxel was found to be effective and tolerable in advanced NSCLC patients with IPF. Moreover, nintedanib in combination with such chemotherapy improved overall survival in patients with nonsquamous histology.

Considering the increasing number of identified driver oncogene alterations, additional genetic tests are required to determine the treatment for advanced non‐small‐cell lung cancer (NSCLC). Next‐generation sequencing can detect multiple driver oncogenes simultaneously, enabling the analysis of limited amounts of biopsied tissue samples. In this retrospective, multicenter study (UMIN ID000039523), we evaluated real‐world clinical data using the Oncomine Dx Target Test Multi‐CDx System (Oncomine DxTT) as a companion diagnostic system. Patients with NSCLC who were tested for a panel of 46 genes using the Oncomine DxTT between June 2019 and January 2020 were eligible for enrollment. Patients from 19 institutions affiliated to the West Japan Oncology Group were recruited. The primary endpoint of the study was the success rate of genetic alteration testing in four driver genes (EGFR, ALK, ROS1, and BRAF) using the Oncomine DxTT. In total, 533 patients were enrolled in the study. The success rate of genetic alteration testing for all four genes was 80.1% (95% CI 76.5%‐83.4%). Surgical resection was associated with the highest success rate (88.0%), which was significantly higher than that for bronchoscopic biopsy (76.8%, P = .005). Multivariate analysis revealed a significant difference for surgical resection alone (P = .006, 95% CI 1.36‐6.18, odds ratio 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings.

There have been few data on the chemotherapy in elderly advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS), and usefulness of chemotherapy for such patients remains unclear. The objective of this study was to identify factors that predicted the survival benefit of chemotherapy. All consecutive elderly patients (≥75 years) with advanced NSCLC, Eastern Cooperative Oncology Group PS ≥2, EGFR mutation wild type/unknown, and newly diagnosed from January 2009 to December 2012 at a tertiary hospital were retrospectively reviewed. We enrolled 59 patients, and 31 patients received at least one chemotherapy regimen (chemotherapy group). However, 28 patients received best supportive care (BSC) alone (BSC group). The proportion of PS 2 and serum albumin levels was significantly higher in the chemotherapy group than in the BSC group. In the chemotherapy group, log-rank testing did not show statistically significant differences in overall survival (OS) between the single-agent therapy group and carboplatin-based doublet therapy group; however, the OS of patients receiving chemotherapy for only 1 cycle (early termination) was significantly shorter than patients receiving chemotherapy for ≥2 cycles. Hypoalbuminemia was not only a risk factor for the early termination of chemotherapy but also an independent prognostic factor in the chemotherapy group. A receiver operating characteristic curve analysis showed that the best cut-off value was 3.40 g/dL. In patients with serum albumin levels ≥3.40 g/dL, OS was significantly better in the chemotherapy group than in the BSC group (p = 0.0156), however, patients with serum albumin levels <3.40 g/dL exhibited poor prognosis regardless of the presence or absence of chemotherapy. In the elderly NSCLC patients with poor PS, serum albumin levels may help identify certain patient populations more likely to receive a survival benefit of systemic chemotherapy.