KRAS A59T

The single case treated with immunotherapy showed complete and sustained response with regression of bone metastases despite abnormal beta-catenin/CTNNB1, which has been associated with immunotherapeutic resistance. These data suggest that the SB-GN pattern may connote a poor prognosis even in the absence of overt pilomatrix-like differentiation, and that novel molecular events may have implications for the treatment of these tumors.

KRAS mutated CRC patients in North Africa have been identified with incidence closer to the European figures. Beside established anti-CRC treatment, better understanding of the causality of CRC can be established by combining epidemiology and genetic/epigenetic on CRC etiology. This approach may be able to significantly reduce the burden of CRC in North Africa.

Pts received RETi after a median number of 1 treatment line (range 0‐6) and 83% had received vandetanib (V) prior to RETi... By‐pass resistance MA may be the most frequent mechanism of progression under RETi. More aggressive histology may arise following proghression; further explorations are warranted.

Erlotinib induced partial response; May 2021 started osimertinib therapy. RET fusion occurs in 1–2% of NSCLC, particularly in younger non‐smokers and high risk for brain metastasis is established. MEN2B/MEN1/MEN2A germline mutations have to be considered when RET mutations present low allele frequency; tumoral heterogeneity will always be considered if RET mutations in follow up with higher frequency. NGS cfDNA potentiality for actionable RET mutations, identification, as well as resistance mechanisms after initial response/resistence rearranged RET.

Our results demonstrate the potential of small multigene panels that can be used in diagnostics for the detection of rare therapeutically relevant variants. Moreover, the division of patients into groups based on the presence of APC and TP53 mutations enables this panel to be used in retrospective studies on the effectiveness of treatment with anti-EGFR inhibitors.

A59T was also detected in 11 additional cancer types, most prominently in cases of gynecologic or other gastrointestinal sites of origin. This study provides supportive evidence that A59T, and possibly other similarly rare KRAS variants, co-occur with predictive biomarkers of response to immunotherapy.

We establish single-agent cetuximab efficacy in optimally selected patients and show that subclonal RAS/BRAF alterations are uncommon and remain of indeterminate significance.

Elucidation of differential effector engagement responsible for the variable phenotypic readouts of the mutants is warranted. If validated by mouse studies and clinical correlates, these can have wider implications in choosing treatment options.