CHICAGO (GenomeWeb) – Targeting actionable genetic mutations identified by tumor genomic profiling may slightly boost survival time in individuals with advanced cancer, though there are still challenges accessing molecularly tailored treatments for individuals with such mutations.
At the American Society of Clinical Oncology annual meeting here on Saturday, Olivier Tredan, medical oncology chair at the Centre Leon Berard in Lyon, France, outlined preliminary findings from the ProfiLER study, a clinical trial focused on molecular profiling for individuals with advanced cancer that has so far enrolled nearly 2,700 individuals with advanced forms of breast cancer, colorectal cancer, gynecological cancer, head and neck cancer, sarcoma, or other cancer types.
The team has analyzed tumor samples from 1,944 of the these individuals, using a combination of copy number profiling by array-based whole-genome hybridization and targeted exon sequencing to unearth point mutations in dozens of cancer-related genes, Tredan explained during a press briefing. Another 416 individuals had to withdraw due to low DNA availability, a lack of exploitable tumor sample, and similar technical factors.
The researchers uncovered one or more actionable mutations in 1,004 individuals — just shy of 52 percent of those whose tumors were profiled. Though they unearthed only one actionable mutation in many of the cases, nearly 400 individuals had two or more apparently actionable mutations.
Alterations in the PIK3CA/mTOR pathway were most common, Tredan noted, though the investigators also identified mutations affecting genes such as CDKN2A, KRAS, CCND1, PTEN, and many others.
During its weekly meetings, the project's multidisciplinary molecular tumor board went over such genomic findings alongside individuals' clinical data and other considerations, Tredan explained, coming up with mutation-targeted treatment recommendations for 676 of the advanced cancer patients.
But despite those recommendations, just 143 of the patients actually received targeted treatment — a discrepancy that Tredan attributed to everything from lack of access to appropriate targeted agents or previous treatment with the recommended drug to patient health declines or early death before targeted treatment could be attempted.
In the group of individuals who did receive the recommended targeted treatment, the team saw a slight uptick in survival: the three-year-survival rate climbed to nearly 54 percent compared with 46 percent survival after five years in the group that did not get targeted therapy. Likewise, survival in the targeted treatment group was almost 35 percent after five years and 28 percent in the non-targeted group.
Though such results are encouraging, Tredan cautioned that the study was not intended to compare survival as a primary endpoint. The work highlights ongoing challenges in obtaining potentially useful targeted treatments for patients with actionable mutations in their tumors, City of Hope's Sumanta Kumar Pal told reporters, while commenting on the ProfiLER study and its potential implications.