Immunotherapy

There are small studies that suggest that exon 18 mutations (unlike most common EGFR mutations) could be sensitive to immunotherapy.

Here are the links to the studies:

1) Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR‐mutated non‐small cell lung cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488155/      27 patients in the study - 7 patients out of them with uncommon mutations and 4 patients out of them with G719X mutation - patients with uncommon mutations achieved durable response (see graphs)

Of various clinical parameters, only patients with uncommon EGFR mutations, including G719X in exon 18 and insertion in exon 20, significantly correlated with responding to ICIs, compared to those with common EGFR mutations (hazard ratio of 0.047 with 95% confidence interval of 0.004‐0.557, P = 0.015) (Figure (Figure1B,C,1B,C, Table Table2).2). Although the PD‐L1 TPS in tumors, smoking status, and location of metastatic lesions were known to be predictive factors for therapeutic effects of ICI treatment in NSCLC with wild‐type EGFR, there were no significant differences in this study.

2) P2.07-003 Nivolumab for Patients with EGFR Mutation-Positive Non-Small Cell Lung Cancer
https://www.jto.org/article/S1556-0864(17)32936-2/pdf

https://academic.oup.com/annonc/article/29/3/777/4638418

Three patients achieved durable disease control lasting more than 1 year, two of them with G719X

3) Effect of pembrolizumab on patients harboring uncommon epidermal growth factor receptor mutations

https://www.annalsofoncology.org/article/S0923-7534(19)34551-X/fulltext

https://www.jto.org/article/S1556-0864(18)32617-0/fulltext

- pembrolizumab (Keytruda) was effective for 3 patients (male ex-smokers) with exon 18 G719X with high PD-L expression