EGFR L747_A750delinsP

Conclusions : To our knowledge, this is the largest liquid biopsy analysis comparing common/uncommon ex19dels in NSCLC and shows similar genomic findings across groups. Further work should be done to explore additional genomic and non-genomic factors to aid in patient selection for EGFR TKIs for uncommon findings.

Five-year survival rate for patients with EGFR-mutant metastatic lung adenocarcinoma treated with Erlotinib or Gefitinib have been reported to be up to 15%, and ex19dels, non-smoking habit, and absence of extrathoracic or brain metastases have previously been associated with prolonged survival. The current case fits well into that in general. However, most such patients need several lines of medical antineoplastic therapy, radiotherapy or have had previous surgery, neither of which has been the case for our patient.

The EGFR exon 19 deletion-insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.

These differences did not reach statistical significance, possibly related to the small sample size. Future work will involve expanding our multi-institutional collaboration and investigating osimertinib efficacy for other uncommon exon 19 deletion subtypes.

This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

We found one classic EGFR activing mutation (L747_A750delinsP) and one MAP2K1 activating mutation (F53_Q58delinsL), which can be targeted by EGFR-TKIs and MEK inhibitor trametinib, respectively...We also found STK11/TSC2 inactivating mutations and a dominant-negative mutation of PTEN (R130Q) which could be targeted by mTOR inhibitor everolimus and AKT inhibitor capivasertib, respectively... The mutational landscape of our PDAC cohort provided compelling evidence that targetable driver mutations accounted for a significant portion of KRAS wide-type tumors . Our findings demonstrated that genomic profiling of PDAC patients can enable physicians to optimize their clinical management and enroll them into genomically matched clinical trials.