Angela Lamarca, MD, PhD
Angela Lamarca, MD, PhD, of the Christie NHS Foundation Trust, Manchester, United Kingdom, served as European Society for Medical Oncology (ESMO) commentator for the ClarIDHy trial in a press briefing held during the ESMO Congress 2019. Dr. Lamarca acknowledged, “The reported median progression-free survival may seem short, and some people may question whether this is clinically meaningful. However, for researchers working in cholangiocarcinoma, it is a breakthrough.”
She added, “A treatment that increases the chance of being free from disease progression by 30% at 6 months and that prolongs survival from 6 months to 10.8 months [after adjusting for crossover] is definitely meaningful for our patients and their families.”
ClarIDHy Commentary
Ian Chau, MD, Consultant Medical Oncologist with the Gastrointestinal and Lymphoma Units of The Royal Marsden NHS Foundation Trust in London and Surrey, United Kingdom, discussed ClarIDHy at the Presidential Symposium where it was presented. His key takeaway was that advances are being made in treating cholangiocarcinoma, based on the identification of molecular subtypes within this rare tumor.
“Molecular testing should be standard, and not just in the second line, but also in the first,” Dr. Chau maintained. “The study also shows that it’s feasible to do randomized controlled trials in subgroups of rare cancers.” He noted that the intent-to-treat analysis found only a trend favoring ivosidenib in overall survival, but in the adjusted analysis, the survival difference became statistically significant (hazard ratio = 0.46; P < .001). “Perhaps this is the true value. It depends on which method we believe.”
Although ivosidenib produced side effects, he noted the absence of differentiation syndrome, which is a problem in acute myeloid leukemia. Quality of life was reported to be better with ivosidenib. However, “health-related quality of life is a multidimensional assessment,” Dr. Chau noted, and he questioned the lack of data reported for all four instruments employed. Altogether, ivosidenib improves progression-free survival in IDH1--mutated cholangiocarcinoma and may improve overall survival, he concluded. But it does increase toxicities and has an unclear effect on quality of life.
Commentary on FIGHT-202
Discussing FIGHT-202 at the ESMO Congress, Per Pfeiffer, MD, PhD, Professor of Oncology at Odense University Hospital in Denmark, also applauded the investigators for enrolling so many patients with a rare disease. He agreed with Dr. Chau on the value of identifying genetic subtypes of cholangiocarcinoma and creating roles for drugs that target distinct mutations. As for the FGFR genetic alterations, he explained that 23 ligands stimulate four FGFR family members, and the FGF/FGFR signaling pathway plays a central role in multiple cellular processes by stimulating proliferation, cell migration, and angiogenesis. Gene fusions and rearrangements are oncogenic drivers.
Per Pfeiffer, MD, PhD
FIGHT-202 showed promising results: a 3% complete response rate, a 33% partial response rate, and “a very impressive” 82% disease control rate, with a median progression-free survival of 6.9 months and a median overall survival of 21.1 months. These data are in line with those of several small phase I and phase II studies of other FGFR inhibitors, Dr. Pfeiffer noted.
“Personalized therapy is important … and FGFR inhibition in patients with FGFR fusions/rearrangements is promising,” he concluded. “The biggest challenge will probably be to identify patients.” ■
DISCLOSURE: Dr. Lamarca has received honoraria or consulting fees from Eisai, Nutricia, Ipsen, and QED; has been a member of speakers bureaus for Pfizer, Ipsen, Merck, and Incyte; and has received travel or educational funding from Ipsen, Pfizer, Bayer, Advanced Accelerator Applications, Sirtex, Novartis, Mylan, and Delcath. Dr. Chau has been a consultant or advisor for AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Merck Serono, MSD Oncology, Oncologie International, Pierre Fabre, and Roche/Genentech; and has received honoraria from Lilly and travel expenses from Bristol-Myers Squibb, Lilly, Merck Serono, and MSD, as well as research funding from numerous companies. Dr. Pfeiffer has served as a consultant or advisor for and received research funding from Merck Serono and Roche.
