medwireNews: Genomic alterations in CDKN2A are associated with worse clinical outcomes in patients with advanced urothelial carcinoma treated with immune checkpoint inhibitors (ICIs), report US researchers.
Therefore, “CDKN2A alteration status may serve as a predictive biomarker” in this patient population, they said in the abstract of a poster presented at the 2021 Genitourinary Cancers Symposium.
Amin Nassar (Brigham and Women's Hospital, Boston, Massachusetts) and colleagues identified 2039 patients with one of six tumor types who received ICI treatment either at the Dana-Farber Cancer Institute (DFCI) in Boston or at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA, and had available sequencing data.
The included histologies were esophagogastric cancer, head and neck cancer, melanoma, non-small-cell lung cancer, renal cell carcinoma, and urothelial carcinoma. The majority (82.6–84.3%) of patients in the DFCI and MSKCC cohorts had received single-agent ICI therapy.
In the DFCI cohort, multivariable analysis adjusting for prior lines of treatment and tumor mutational burden showed a significant association in urothelial cancer patients between the presence of CDKN2A alterations (loss of function mutations or homozygous deletions) and worse overall survival (OS), time to treatment failure (TTF), and objective response rate (ORR), with hazard ratios (HRs) of 2.0, 2.2, and 4.0, respectively.
The association between CDKN2A alterations and worse OS in urothelial cancer was replicated in the MSKCC cohort, with an HR of 1.7 after adjustment for type of therapy and tumor mutational burden.
Of note, CDKN2A alterations did not appear to be predictive of OS in a cohort of 56 patients who received platinum-based regimens at DFCI.
For the other tumor types, the researchers found significant associations between CDKN2A alterations and some, but not all, assessed outcomes, and in one, but not both, of the cohorts. For instance, CDKN2A alterations in melanoma patients correlated significantly with reduced OS in the DFCI, but not the MSKCC cohort, while the opposite was true for those with esophagogastric cancer and renal cell carcinoma.
And although there was a significant association between CDKN2A alterations in the melanoma subgroup and shorter TTF, no such association was observed for ORR.
The investigators concluded that more work is needed “to discern the biology of CDKN2A alterations” and their interaction with ICIs.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany