As is common in ASCO Annual Meetings, the lung cancer track in ASCO20 Virtual included numerous relevant studies. Some of the most promising results presented this year were from trials of targeted agents.
Tepotinib is a highly selective orally administered MET tyrosine-kinase inhibitor (TKI). Primary efficacy data from the phase II VISION trial of tepotinib in patients with metastatic non-small-cell lung cancer (NSCLC) harbouring MET exon 14 skipping alterations were presented and simultaneously published. In patients with ≥9 months of follow-up (n = 99), the objective response rate (ORR) was 46%, and the median progression-free survival (mPFS) duration was 8.5 months. In patients with brain metastases (11 of 99), the ORR was 55% and the mPFS duration was 10.9 months. The frequency of grade ≥3 treatment-related adverse events (TRAEs) was 28%.
Several presentations focused on combinatorial approaches involving TKIs. A phase I/II trial is testing concurrent treatment with the EGFR TKIs osimertinib and gefinitib to delay emergence of acquired mutations at second sites in EGFR. At a median follow-up of 14.8 months, the ORR was 88.9%, and the disease control rate was 100.0% in 27 evaluable patients. In a phase III trial involving 133 patients with untreated oligometastatic NSCLC (<6 lesions), stereotactic body radiotherapy plus a TKI improved outcomes over treatment with a TKI alone: the mPFS duration was 20.2 months versus 12.5 months (HR 0.62, 95% CI 0.39–0.97; P < 0.001), and the median overall survival (mOS) duration was 25.5 months versus 17.4 months (HR 0.68, 95% CI 0. 47–1.00; P < 0.001). Grade 3–4 TRAEs were more frequent with combination therapy.
Use of TKIs in the adjuvant setting in patients with EGFR-mutated NSCLC was another important theme. In the phase III ADJUVANT-CTONG1104 trial involving 111 patients, mOS durations were numerically, but not significantly, longer with gefitinib versus doublet chemotherapy (75.5 months versus 62.8 months; HR 0.92, 95% CI 0.62–1.36; P = 0.67). In the phase III ADAURA trial, 2-year disease-free survival was higher with osimertinib versus placebo (90% versus 44%; HR 0.17, 95% CI 0.12–0.23; P < 0.0001).
Therapeutic approaches based on HER2 targeting are being tested in patients with NSCLC. Interim data of the phase II DESTINY-Lung01 trial of the antibody–drug conjugate trastuzumab deruxtecan revealed an ORR of 61.9% and grade ≥3 TRAEs in 52.4% of patients.
Trials of immune-checkpoint inhibitors were also discussed. The OS benefit of nivolumab plus ipilimumab (with or without chemotherapy) over chemotherapy in the metastatic setting was confirmed in CheckMate 227 and CheckMate 9LA. Results after 5 years of follow-up as well as those from biomarker analyses are eagerly awaited.
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Romero, D. Lung cancer at ASCO20 Virtual. Nat Rev Clin Oncol 17, 450 (2020). https://doi.org/10.1038/s41571-020-0405-z