Metastatic non-colorectal cancers have adverse prognosis and no target or immunotherapy is approved until now. NGS platforms are supposed to be useful tailoring systemic treatments and/or screening patients(pts) for early phase clinical trials. Although attractive, NGS-tailored therapies (NGS-TT) can have disappointing results in not approved indications outside clinical trials. In this analysis we evaluated the tumor genetic profiles including potential germline mutations, suggested therapies, available clinical trials, and the results for off-label NGS-TT.
we performed a retrospective assessment of clinical and molecular characteristics, NGS-TT prescribed and responses in a cohort of MNCGIC evaluated through the 315 genes NGS platform between 2013-2019. We looked for potential germline mutations in mismatch-repair genes and BRCA1/2, as well as the TP53R337H founder mutation.
among 78 pts, the median age was 58.5y (20-79), with 51 (65%) males and 27 (35%) females. The most common sites were pancreas (41%), stomach (15.4%) and biliary tract (15,4%); 83% were ECOG 0/1, with up to 2 lines of therapy (60.25%). Mean number of altered genes was 4.41 (1-19) and tumor mutational burden (TMB) was assessed in 24 pts, with 79% TMB-low (mean 5.22 muts/Mb). Ten pts (12.85%) underwent off-label NGS-TT after discussion at multidisciplinary tumor boards; among 9 available for response evaluation, 7 experienced progression as best response. Clinical trials were suggested for 73 pts (93,6%), but only one patient (pt) was referred to it, since all trials where abroad. We also identified 3 cases for which germline sequencing would be of value (1 pt with TP53 R337H mutation; 2 young gastric cancer pts: one with concurrent MSH6/BRCA2 mutations and another with MLH1truncation exon10 alteration).
in our cohort, the adoption of NGS to tailor systemic treatment did not show an important impact for MNCGIC pts. Increase participation of developing country centers in clinical trials is strongly needed. Potentially germline mutations were present in this series and deserve further investigation.
The authors.
Has not received any funding.
D. de Freitas: Honoraria (self): Roche. D.L.F. Jardim: Honoraria (self): Foundation Medicine. B. Gumz: Honoraria (self): Novartis. All other authors have declared no conflicts of interest.