Lancet Respiratory Medicine最新文献

Background: Neoadjuvant immunotherapy with chemotherapy improves outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Given its immunomodulating effect, we investigated whether stereotactic body radiotherapy (SBRT) enhances the effect of immunochemotherapy.

Methods: The SACTION01 study was a single-arm, open-label, phase 2 trial that recruited patients who were 18 years or older and had resectable stage IIA-IIIB NSCLC from the Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients received SBRT (24 Gy in three fractions) to the primary tumour followed by two cycles of 200 mg intravenous PD-1 inhibitor, tislelizumab, plus platinum-based chemotherapy. Surgical resection was performed 4-6 weeks after neoadjuvant treatment. The primary endpoint was major pathological response (MPR), defined as no more than 10% residual viable tumour in the resected tumour. All analyses were conducted on an intention-to-treat basis, including all patients who were scheduled for neoadjuvant treatment. The trial was registered with ClinicalTrials.gov (NCT05319574) and is ongoing but closed to recruitment.

Findings: Between May 18, 2022, and June 20, 2023, 46 patients (42 men and four women) were enrolled and scheduled for neoadjuvant treatment. MPR was observed in 35 (76%, 95% CI 61-87) of 46 patients. The second cycle of immunochemotherapy was withheld in four (9%) patients due to pneumonia (n=2), colitis (n=1), and increased creatinine (n=1). Grade 3 or worse adverse events related to neoadjuvant treatment occurred in 12 (26%, 95% CI 14-41) patients. The most frequent treatment-related adverse event (TRAE) was alopecia (16 [35%] patients), and the most frequent grade 3 or worse TRAE was neutropenia (six [13%]). There was one treatment-related death, caused by neutropenia. No deaths within 90 days of surgery were reported.

Interpretation: Preoperative SBRT followed by immunochemotherapy is well tolerated, feasible, and leads to a clinically significant MPR rate. Future randomised trials are warranted to support these findings.

Funding: BeiGene.

Background: Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC.

Methods: This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual.

Findings: Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1).

Interpretation: Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC.

Funding: HUTCHMED and AstraZeneca.