In September 2022, the FDA granted approval to a third FGFR2-targeted therapeutic, futibatinib (Lytgobi) for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma that tests positive for FGFR2 fusions or other rearrangements. The approval was based on the results of a phase I/II clinical trial that showed that futibatinib shrank tumors in 42 percent of patients (400). The median duration of response was 9.7 months. Futibatinib works differently than pemigatinib and infigratinib and preliminary data indicate that it may mitigate the challenge of treatment resistance since patients who had disease progression after prior FGFR-targeted therapy with other inhibitors maintained sustained clinical benefit with futibatinib (400). Combining Molecularly Targeted Therapeutics to Block Tumor Growth The BRAF enzyme has a critical role in controlling cell growth. The BRAF gene is altered in approximately six percent of all human cancers, including melanoma and colorectal cancer (402). Most cancer-related changes in the BRAF gene cause the protein to continuously stay active, thus helping cancer cells grow faster than normal cells. One of the most common cancerrelated changes is the BRAF gene is called the BRAF V600E mutation. Presence of the BRAF V600E mutation is associated with poor outcomes for patients with certain types of cancer. The Challenges Posed by Rare Cancers Rare cancers affect fewer than 40,000 people per year in the U.S. All childhood cancers are considered rare cancers. Rare cancers pose significant challenges to patients, physicians, and researchers. According to the NCI, these challenges include: FOR PATIENTS Finding a physician It is hard to find a physician who knows a lot about the rare cancer with which they have been diagnosed and how to treat it. Treatment proximity It is necessary to travel far to get treatment for a rare cancer. Long diagnosis time It takes a long time from when they first notice a symptom to the time when doctors know that the symptom is caused by a rare cancer and what type of cancer it is. FOR PHYSICIANS Lack of training They have not been trained to treat a rare cancer with which their patient has been diagnosed. Unsure expectations They do not know what to tell their patient about what to expect with the rare cancer. Finding expert help They are unable to find an expert who can answer their questions about the rare cancer with which their patient has been diagnosed or identify someone to whom they can refer the patient. FOR RESEARCHERS Lack of information There is no information about the rare cancer they are investigating to give ideas on how to go about tackling the disease. Lack of research models There are no animal or cell models of the rare cancer they are investigating in which to test their ideas. Lack of biospecimens There are not enough tumor samples from patients with the rare cancer they are investigating for their research. Lack of patients There are not enough patients with a given rare cancer to conduct a clinical trial testing a potential new treatment. The National Cancer Institute has launched several initiatives with the goal of accelerating the pace of basic, translational, and clinical research in rare cancers. As one example, the My Pediatric and Adult Rare Tumor network (MyPART) is a group of scientists, patients, family members, advocates, and health care providers working together to find treatments for rare cancers in children, teens, and young adults faster. SIDEBAR 36 AACR Cancer Progress Report 2023 Advancing the Frontiers of Cancer Science and Medicine 90
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