Abstract
Final results from MOSCATO-01, a prospective precision medicine–based trial, indicate that molecular profiling improves outcomes for patients with diverse types of advanced cancer. Compared with previous nontargeted therapy, progression-free survival was extended by 30% in a third of patients whose treatment was tailored to their tumor's genetic makeup.
According to final results from the prospective MOSCATO-01 trial, tailoring treatment to the genetic makeup of a patient's tumor improves progression-free survival (PFS), compared with previous nontargeted therapy. Lead investigator Jean-Charles Soria, MD, PhD, of the Institut Gustave Roussy in Villejuif, France, reported the data at the Molecular Analysis for Personalized Therapy conference in London, UK, in September.
Soria and his colleagues biopsied a total of 949 patients for this study. A diverse range of advanced cancers were represented, including bladder carcinoma, head and neck squamous cell carcinoma, and bile duct cancer; all patients had received a median of three prior therapies for their disease. In 844 cases, the tumor tissue samples were of sufficient quality to undergo extensive molecular analyses, including DNA sequencing with a customized 75-gene panel, comparative genomic hybridization to assess copy-number variations, and RNA sequencing.
The investigators looked at whether the PFS achieved with targeted therapy was better than that seen with prior standard treatment. “Our primary objective was to demonstrate that using molecular profiling to guide therapeutic decisions would extend progression-free survival by 30% in at least 25% of patients,” Soria explained. His team uncovered potentially actionable targets in 411 of the patients profiled; aberrations in the FGFR, PI3K/AKT, HER, and Notch pathways were the most common.
The investigators then matched 199 of these patients with targeted treatments. Most were enrolled in one of the 60 ongoing phase I trials at Institut Gustave Roussy, Soria said, but a few cases involved off-label use of drugs indicated for other cancer types. The remaining 212 patients were excluded from the study, either because their actionable mutations were well established, with approved agents available—for instance, ALK inhibitors for ALK-translocated non–small cell lung cancer—or because there were no suitable phase I trials at the time.
Soria reported that MOSCATO-01 achieved its primary endpoint and is the first study of its kind to show that precision medicine works: Of 193 evaluable patients, 33% experienced an extended PFS of 30% with tailored therapy, compared with previous treatments. Overall survival (OS) also improved, he noted, citing patients with alterations in HER3 as an example. The median OS was 8 months for patients who received non–HER-specific therapy, and not reached for those given trastuzumab (Herceptin; Roche) or afatinib (Gilotrif; Boehringer Ingelheim), both inhibitors of HER-family signaling.
The team is now turning its attention to two other prospective precision medicine–based trials for lung cancer and breast cancer, respectively. Both SAFIR-02 studies will evaluate the utility of molecular profiling in selecting maintenance therapy for patients with advanced but stable disease, who will be randomly assigned to receive either a targeted agent or standard chemotherapy.
MOSCATO-02 is also in the works, Soria said. This time around, he and his group have added analyses of different tumor-infiltrating immune cell populations “to enrich our molecular readout and enable optimal triage of patients toward the relevant phase I studies.” –Alissa Poh
For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.
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