Clinical outcomes of a quadruplet regimen (immunotherapy, chemotherapy, anti-angiogenic therapy) in non-small cell lung cancer with EGFR exon 20 insertion mutations: a case series.

BACKGROUND: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations represent a non-classical subtype within EGFR-mutated non-small cell lung cancer (NSCLC), with patients historically showing poor responses to immunotherapy. However, trials such as IMpower150 and ORIENT-31 have demonstrated that adding an anti-angiogenic agent to immunotherapy and chemotherapy can improve outcomes in the broader population of EGFR-mutant NSCLC. This provides a rationale for evaluating a similar quadruplet strategy specifically in the ex20ins subset.

CASE DESCRIPTION: We present six cases of advanced EGFR ex20ins-mutated NSCLC treated at Chinese PLA General Hospital with the quadruplet regimen. Four received it as first-line therapy, and two as second-line therapy after targeted agents. Four out of six patients achieved a partial response (PR). The median progression-free survival (PFS) was 14.7 months [95% confidence interval (CI): 2.1-27.3], and the mean overall survival (OS) was 34.2 months (95% CI: 17.5-50.9). Treatment-related adverse events (TRAEs) were common but manageable. Hematological toxicities, including neutropenia and anemia, occurred in all six patients. Non-hematological TRAEs included hypertension (in five patients), gastrointestinal reactions (in three patients), and abnormal liver function (in two patients). All were grade one to two, with no discontinuations due to toxicity.

CONCLUSIONS: This small case series describes preliminary antitumor activity and a manageable safety profile with the quadruplet regimen in EGFR ex20ins-mutated NSCLC, warranting further investigation.