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Genomic testing may guide personalized care for advanced cancer
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CHICAGO — Routine genomic testing of tumor samples appears feasible and enabled more personalized treatment, according to the results of the ProfiLER study conducted in France and presented at the ASCO Annual Meeting.
However, only a subset of patients with cancer benefit from this type of testing.
“This study confirms that comprehensive genomic profiling can be performed in routine practice to select patients for targeted cancer therapies,” Olivier Tredan, MD, PhD, chair of the department of medical oncology at Centre Léon-Bérard in France, said in a press release.
Tredan and colleagues analyzed DNA samples extracted from 1,676 patients (55% women; median age, 59 years; range, 1-90) with advanced cancer using targeted exon sequencing of 70 cancer-related genes and whole-genome array comparative genomic hybridization.
Tumor types included colorectal (10.3%), gynecologic (9.5%), breast (8.8%), head and neck carcinomas (7.1%), brain tumors (6.5%) and sarcomas (7.1%).
Researchers analyzed a total of 1,944 patient tumors at the time of the analysis, with 12% ongoing (n = 301).
Among all patients, 609 had only one actionable mutation, and 394 had at least two, with some patients harboring up to six. These included substitutions and small indel mutations (55.3%), amplifications (42.1%) and homozygous deletions (25.5%).
The most common actionable mutations included CDKN2A HD (9.5%) and KRAS (8.5%), followed by P1K3CA (8.2%), CCND1 (5.3%), FGFR1 (3.1%), MDM2 (2.9%), PTEN (2.7%), HER2 (2.3%) and HER1 (2.2%).
The molecular tumor board — a multidisciplinary molecular board of experts that review genomic testing results — recommended 676 patients receive molecular targeted treatments based on their actionable mutations. Of these, only 143 received recommended treatment — which included patients with gynecologic (28%), gastrointestinal (18%) and breast (12%) cancers — with others unable to undergo treatment due to rapid progression of disease, ineligibility for clinical trials or difficulty obtaining available therapies.
These targeted therapies included mTOR inhibitors (39%), antiangiogenic tyrosine kinase inhibitors (21%), EGFR TKI (9.8%) and inhibitors of cell cycles (6.9%).
Of treated patients, the collection of data remained ongoing for 202 patients.
Best responses included complete response (2.3%), partial response (15.1%), stable disease (33.7%) and progressive disease (48.8%).
Median PFS was 2.8 months (95% CI, 2.2-3.5) and 24% of patients achieved 6-month PFS.
A greater proportion of patients remained alive who received recommended targeted therapies than patients who did not at 3 years (53.7% vs. 46.1%) and 5 years (34.8% vs. 28.1%).
“I want to highlight that more than 50% of the tumor had no molecular alterations that are potentially actionable,” Tredan said during the press conference. “However, screening every cancer patient limits the number of patients who can actually receive the molecular agent.”
A new clinical trial — ProfiLER 02 — is planned and will compare the 70-gene test with a commercial 315-gene test. The goal is to determine whether screening a larger number of genes leads to more recommendations for targeted therapy, according to the release.
The study by Tredan and colleagues shows the usefulness of genomic testing in clinical practice and may assist in treatment decisions for patients, according to Sumanta Kumar Pal, MD, co-director of City of Hope’s Kidney Cancer Program, ASCO expert and HemOnc Today Editorial Board member.
“The takeaways for me are to expand repertoire for available targeted therapies and think about implementing molecular testing sooner in trials such as this to afford patients an opportunity to effectively participate,” Pal said at the press conference. – by Melinda Stevens
Reference:
Tredan O, et al. Abstract LBA100. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.
Disclosure: Tredan reports research funding from Bayer, GlaxoSmithKline and Novartis Pharma KK. Please see the abstract for a list of all other researchers’ relevant financial disclosures. Pal reports honoraria or research funding from, or consultant/advisory roles with Astellas Pharma, Aveo, Bristol-Myers Squibb, Exelixis, Genentech, Medivation, Myriad Pharmaceuticals, Novartis and Pfizer.