Purpose: The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR ) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic EGFR mutations.

Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies reporting the efficacy and safety of osimertinib in NSCLC with uncommon EGFR mutations defined as any mutations other than exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Then, we performed a meta-analysis to pool survival outcomes and antitumoral activity, including intracranial (ic) response and adverse events.

Results: Fifteen studies comprising 594 patients were included. The most frequently observed uncommon solitary mutations were G719X in 25% (81/327) of patients and L861Q in 21% (69/327). The most common compound mutations were G719X with T790M in 12% (23/192) of patients and G719X with S768I in 11% (22/192). Pooled analysis showed an objective response rate (ORR) of 51.30% (95% CI, 45.80 to 56.81), a disease control rate (DCR) of 90.11% (95% CI, 86.27 to 92.96), a median progression-free survival of 9.71 months (95% CI, 7.96 to 11.86), and a median overall survival of 16.79 months (95% CI, 9.93 to 28.39). icORR was 45.96% (95% CI, 30.18 to 62.17), and icDCR was 95.76% (95% CI, 69.84 to 100). Osimertinib was well tolerated with a frequency of grade 3 or more adverse events of 21.77% (95% CI, 6.24 to 43.33).

Conclusion: Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.