On this version of ONCOLOGY®, Christine Y. Chung, DO, and colleagues report on the next-generation sequence (NGS) testing status of 77 patients referred to their practice for phase 1 study enrollment. It appears within the case of each neighborhood and educational practices, of their Colorado space referral zone, about half the sufferers had beforehand acquired both tumor or circulating tumor (ct)DNA testing for actionable mutations. Though the authors level out the speed of sequencing is roughly equal within the 2 settings, my query is why physicians are even doing this costly testing.
By The Most cancers Genome Atlas1 dedication of molecular profile for 150 pancreatic cancers, we all know that 93% of sufferers can have KRAS mutations and one other 10% different, often concurrent RAS mutations. TP53 mutations happen 72% of the time, and solely 4% to five% have a BRCA mutation. Different actionable mutations are actually fairly uncommon. For instance, 3% can have BRAF mutations. Additionally, within the SWOG 1513 examine (NCT02890355),2 E. Gabriela Chiorean, MD, and her colleagues confirmed, in a second-line chemotherapy setting, that maybe 30% had some sort of DNA restore faulty gene primarily based on an outlined “HDR” assay, but the addition of a PARP inhibitor to FOLFIRI (folinic acid, 5-FU, oxaliplatin, and irinotecan) was not helpful.
Within the “Know Your Tumor” (KYT) study3 referenced by Chung, the sufferers who had sequencing-informed remedy appeared to do higher. However let’s look additional at these information. Almost 1900 sufferers have been enrolled and 1082 have been sequenced. Solely 667 had final result information and 38% of those have been thought of “actionable,” but many of those are mutations with no identified molecular medication efficient for pancreatic most cancers, together with ATM, AKT2, PALB2, and CDK mutations. The end result information are closely influenced by the only a few with microsatellite instability–excessive tumors, diagnosable with immunohistochemistry—no NGS required—and NTRK fusions. The end result of this so-called actionable group was certainly superior, but what does it signify? It is a noncontrolled trial that maybe tells us that sufferers with DNA restore deficits do higher total, maybe resulting from sensitivity to our present chemotherapy medication. It does inform us little or no past the few actionable mutations we already learn about.
Lastly, we all know that sufferers with germline mutations could also be candidates for olaparib (Lynparza) following induction chemotherapy. Nevertheless, the rules advocate that each one sufferers obtain germline testing. That is cheaper than tumor NGS and even ctDNA testing, and could also be accomplished even by typically obtainable platforms resembling 23andMe. If we carry out tumor NGS to search out BRCA mutations after which later carry out germline testing, this can result in elevated prices to the well being care system. Moreover, the approval to be used of this PARP inhibitor in pancreatic most cancers doesn’t embrace sufferers with somatic BRCA mutations.
A brand new class of RAS inhibitor medication, particularly focusing on KRAS G12C is now within the clinic. These medication are exhibiting exercise in non–small cell lung most cancers and probably shall be lively in colon most cancers. As soon as these medication and others focusing on extra frequent KRAS mutations have been proven efficient for pancreatic most cancers, there shall be a superb motive to carry out NGS testing on all sufferers with pancreatic most cancers. In the intervening time, NGS testing is an costly take a look at that might price the well being care system over $200 million yearly, if all 60,000 circumstances of newly identified pancreatic most cancers have been examined. Personally, I’m wanting ahead to when this shall be an economical expertise.
1. Most cancers Genome Atlas Analysis Community. Built-in genomic characterization of pancreatic ductal adenocarcinoma. Most cancers Cell. 2017;32(2):185-203.e13. doi: 10.1016/j.ccell.2017.07.007
2. Chiorean EG, Guthrie KA, Philip PA, et al. Randomized part II examine of second-line modified FOLFIRI with PARP inhibitor ABT-888 (Veliparib) (NSC-737664) versus FOLFIRI in metastatic pancreatic most cancers (mPC): SWOG S1513. J Clin Oncol. 2019;37(suppl 15):4014. doi:10.1200/JCO.2019.37.15_suppl.4014
3. Pishvaian M, Blais E, Brody J, et al. Total survival in sufferers with pancreatic most cancers receiving matched therapies following molecular profiling: a retrospective evaluation of the Know Your Tumor registry trial. Lancet Oncol. 2020;21(4):508-518. doi: 10.1016/S1470-2045(20)30074-7