NGS Results in Improved Survival Among Patients With Biliary Tract Cancers

As precision therapy continues to make an impact on outcomes in a myriad of cancers, researchers have published findings that could have important implications for biliary tract cancers, which are rare but aggressive. The findings indicate that relying on circulating tumor DNA (ctDNA) and tissue DNA tests are complementary measures that can better match patients with appropriate therapies.

Appropriately matching these patients with therapies also translates into survival benefit, with the researchers observing significantly longer progression-free survival (PFS). Patients that were matched to therapies based on next-generation sequencing (NGS) had a median PFS of 4.3 months compared with a median PFS of 3 months among patients not matched to therapies. These patients also had a higher disease control rate (61% vs 35%).

“Importantly, the matched regimens remained significantly associated with better PFS even when age, sex, performance status, tumor type, extent of disease, presence of prior radical surgery, number of prior regimens and the number of drugs administered were considered as confounding factors in the multivariate analysis,” wrote the researchers.

Among the 121 patients with biliary tract cancers included in the study, 80 were put on systemic therapies following the molecular profiling, 43% of whom received at least 1 drug that was matched to their profiling results. These matched therapies included therapies targeting alterations in ctDNA and/or tissue-DNA (29 patients), PD-L1 (3 patients), mismatch repair deficiency (1 patient), and a combination of molecular targeting therapy with immunotherapy (1 patient).

Using NGS, the researchers found that of 121 patients, 71 (59%) had ctDNA, 90 (74%) had tissue-DNA, and 40 (33%) had both. Among these 40 patients, there was higher overall concordance between ctDNA and metastatic site tissue-DNA than between ctDNA and primary tumor DNA (78% vs 65% for TP53, 100% vs 74% for KRAS and 100% vs 87% for PIK3CA [but not statistically significant]).

“Interestingly, 76% of the patients had at least one characterized ctDNA alteration while 100% had at least one characterized alteration found in tissue-DNA,” wrote the researchers. “In addition, the median number of alterations per patient (range) was two (0-9) in ctDNA and four (1-9) in tissue-DNA.”

The most common alterations were observed for ctDNA were in TP53 (38%), KRAS (28%), and PIK3CA (14%) and for tissue-DNA were in TP53 (44%), CDKN2A/B (33%) and KRAS (29%). There was a total of 147 characterized alterations identified for ctDNA and a total of 362 characterized alterations observed in tissue-DNA.

Reference

Okamura R, Kurzrock R, Mallory R, et al. Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers. Int J Cancer. Published online July 23, 2020. doi: 10.1002/ijc.33230.