Broad 324-Gene Panel Identifies More Matched Therapies but No Outcome Gain in Advanced Cancers
In a multicenter randomized trial of 741 patients with advanced solid tumors, a 324-gene panel (FoundationOne CDx) identified molecular-based recommended therapies in 51.6% of patients versus 36.9% with an 87-gene panel, a significant 14.8 percentage-point increase. However, no differences in PFS, response rate, or duration of response were observed, raising questions about the clinical benefit of broader panels in heavily pretreated populations.
The original study
Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial.
- Authors
- Trédan O, Pouessel D, Penel N, Chabaud S, Gomez-Roca C, Delord JP, et al.
- Journal
- Nature medicine
- Type
- Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial
- PMID
- 40195451
Original abstract
Large genomic programs have contributed to improving drug development in cancer. To assess the potential benefit of using larger gene panels to guide molecular-based treatments, we conducted a multicenter randomized trial in patients with advanced and/or metastatic solid cancer. Molecular alterations were determined using either a panel of 324 cancer-related genes (Foundation OneCDX (F1CDX)) or a limited panel of 87 single-nucleotide/indel genes and genome-wide copy number variations (CTL) and reviewed by a molecular tumor board to identify molecular-based recommended therapies (MBRTs). Using paired data from both panels for each patient, the primary endpoint was the proportion of patients with an MBRT identified. Main secondary endpoints included the number of patients with at least one actionable alteration leading to MBRT identification, the number of patients with and without MBRTs initiated, progression-free survival, best overall response, duration of response and safety. Among the 741 patients screened, 45.7% had quality-checked tumor samples. MBRTs were identified with F1CDX in 175 (51.6%) patients and with CTL in 125 (36.9%) patients, translating to a significant increase of 14.8 percentage points (P < 0.001) with the more comprehensive gene panel versus the more limited panel, meeting the primary endpoint. However, no differences in clinical outcomes were observed in these patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations. These findings illustrate the potential for larger gene panels to increase the number of molecularly matched therapies. Larger studies are needed to assess the clinical benefit of expanded MBRTs. ClinicalTrials.gov registration: NCT03163732 .