To evaluate the efficacy and safety of osimertinib plus bevacizumab for previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations. We conducted a randomized, open-label, phase 2 study at 21 institutions in Japan. Previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations received either osimertinib (80 mg, daily) plus bevacizumab (15 mg/kg, every 3 wk) or osimertinib monotherapy, and were stratified according to sex, stage, and EGFR mutation status. The primary end point was progression-free survival (PFS) in the intention-to-treat population, assessed by means of blinded, independent central radiologic review. Between January 2018 and September 2018, a total of 122 patients were enrolled (osimertinib + bevacizumab arm, 61 patients; osimertinib monotherapy arm, 61 patients). At a median follow-up duration of 19.8 months, the median PFS was 22.1 months for osimertinib plus bevacizumab and 20.2 months for osimertinib monotherapy, with a hazard ratio of 0.862 (60% confidence interval: 0.700-1.060, 95% confidence interval: 0.531-1.397, one-sided stratified log-rank p = 0.213). Adverse events of grade 3 or worse were observed in 34 patients (56%) in the osimertinib plus bevacizumab arm and 29 (48%) in the osimertinib monotherapy arm. In addition, two (3%) and 11 patients (18%) experienced any grade pneumonitis, respectively, and grade 3 pneumonitis was observed in one patient (2%) in each arm. This study failed to exhibit the efficacy of osimertinib plus bevacizumab for improving the PFS among patients with nonsquamous NSCLC harboring EGFR mutations as first-line treatment.

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.

IMpower010 (ClinicalTrials.gov identifier: NCT02486718 ) previously showed that atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) after adjuvant chemotherapy in patients with resected non–small cell lung cancer (NSCLC). We report DFS final analysis, second overall survival (OS) interim analysis, and safety with a ≥5-year follow-up. Patients with completely resected stage IB-IIIA NSCLC were randomly assigned to atezolizumab (1,200 mg once every 3 weeks, 16 cycles) or BSC after platinum-based chemotherapy. At clinical cutoff (January 26, 2024), stratified hazard ratios (HRs; 95% CI) for DFS were 0.85 (95% CI, 0.71 to 1.01; P = .07) in the intention-to-treat (n = 1,005), 0.83 (95% CI, 0.69 to 1.00) in the all-randomized stage II-IIIA (n = 882), and 0.70 (95% CI, 0.55 to 0.91) in stage II-IIIA PD-L1 tumor cell (TC) ≥1% (n = 476) populations. Stratified HRs (95% CI) for OS were 0.97 (95% CI, 0.78 to 1.22), 0.94 (95% CI, 0.75 to 1.19), and 0.77 (95% CI, 0.56 to 1.06), respectively. The unstratified HRs (95% CI) in the stage II-IIIA PD-L1 TC ≥50% population (n = 229) were 0.48 (95% CI, 0.32 to 0.72) for DFS and 0.47 (95% CI, 0.28 to 0.77) for OS, and the unstratified HRs in the stage II-IIIA PD-L1 TC ≥50% without EGFR / ALK alterations (n = 209) population were 0.49 (95% CI, 0.32 to 0.75) and 0.44 (95% CI, 0.26 to 0.74). No new safety signals were reported. IMpower010 is the first study to report survival outcomes with a ≥5-year follow-up and continued to show benefit with atezolizumab versus BSC after adjuvant chemotherapy in patients with resected stage II-IIIA PD-L1–selected NSCLC.

Although third‐generation epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKI) can overcome T790M‐mediated resistance in non‐small‐cell lung cancer (NSCLC), rebiopsy to confirm T790M status is occasionally difficult. We aimed to investigate the current tendency and the limitations of rebiopsy in clinical practice. This study included 139 consecutive NSCLC patients with EGFR mutations, who had experienced progressive disease (PD) after EGFR‐TKI treatment. We retrospectively reviewed patient characteristics, tumor progression sites and rebiopsy procedures. Of 120 patients (out of the original 139) who were eligible for clinical trials, 75 (63%) underwent rebiopsy for 30 pleural effusions, 32 thoracic lesions, four bone, two liver, and seven at other sites. Rebiopsy procedures included 30 thoracocentesis, 24 transbronchial biopsies, 13 computed tomography (CT)‐guided needle biopsies and 8 other procedures. Of the 75 rebiopsied patients, 71 (95%) were pathologically diagnosed with malignancy; and 34 (45%) had available tissue samples for EGFR analyses. Of the 75 biopsied patients, 61 (81%) were analyzed for EGFR mutation, using tissue or cytology samples; T790M mutations were identified in 20 (33%) of the 61 patients. Of the 120 patients, 45 (38%) did not undergo rebiopsy, because of inaccessible tumor sites (n = 19), patient refusal (n = 6) or decision of physician (n = 10). In conclusion, among patients with EGFR mutations who had PD after EGFR‐TKI treatment, 63% underwent rebiopsy. Most rebiopsy samples were diagnosed with malignancy. However, tissue samples were less available and T790M mutations were identified less frequently than in previous studies. Skill and experience with rebiopsy and noninvasive alternative methods will be increasingly important.

The prognosis of non‐small‐cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) is poor, and 5%‐20% of those receiving chemotherapy experience ILD exacerbation. To evaluate the safety and efficacy of nab‐paclitaxel plus carboplatin for NSCLC patients with ILD, we undertook a multicenter phase II study. Chemotherapy‐naïve patients with advanced NSCLC and mild or moderate ILD received nab‐paclitaxel (100 mg/m², days 1, 8, and 15) plus carboplatin (area under the curve = 6, day 1) every 3 weeks for 4 cycles (maximum, 6 cycles). Interstitial lung diseases were diagnosed based on criteria for fibrosing interstitial pneumonia. The primary endpoint was the prevalence of exacerbation‐free ILD 28 days after completion of protocol treatment. Secondary endpoints were response rate, progression‐free survival, overall survival, prevalence of exacerbation‐free ILD, and toxicity. Ninety‐four patients were enrolled, and 92 patients received any protocol treatment. Median age was 70 years, and 58% had nonsquamous histology. In the primary analysis, the prevalence of exacerbation‐free ILD 28 days after protocol treatment was 95.7% (88/92; 90% confidence interval, 90.3‐98.5), which met the primary endpoint. Response rate was 51% (95% confidence interval, 40%‐62%). At the time of data cut‐off, median progression‐free survival was 6.2 months, and median overall survival was 15.4 months. The most common grade 3/4 adverse events were neutropenia (75%), leukopenia (53%), anemia (48%), and thrombocytopenia (20%). Two treatment‐related deaths (1 each of pulmonary infection and ILD exacerbation) were observed. This study showed that a combination of nab‐paclitaxel with carboplatin was tolerable in NSCLC patients with mild or moderate ILD in terms of safety. This study is registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN 000012989).