The healthcare landscape is changing more rapidly than ever, and daily discoveries in genomics are leading to truly individualized care. During a session at the 42nd Annual Congress in Denver, CO, David Solit, MD, Geoffrey Beene Chair and director of the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at Memorial Sloan Kettering Cancer Center (MSKCC), reviewed cutting-edge genomics science, its role in precision medicine, and innovative genomics programs at his institution. Solit leads a research program that seeks to identify new drug targets using genomic profiling.
Solit outlined the two overarching approaches in genomics research. With the genotype-to-phenotype approach, researchers examine thousands of cancer cells to retrospectively uncover patterns in mutations, which can then be exploited to discover treatments that will work for all patients with that same mutation. Alternatively, with the phenotype-to-genotype approach, researchers identify the genetic basis of a disease based on a rare and extraordinary response that one patient has to a treatment during a clinical trial. In phenotype-to-genotype research, “we have the right drug, we just have to figure out who to give it to,” Solit said.
He reviewed several case studies showing how both approaches have led to significant advances in cancer care. In one dramatic phenotype-to-genotype case, a woman with a rare, small cell ureteral tumor received unsuccessful treatment and surgery, and the disease spread. She was put on a clinical trial and had a very unexpected complete response. However, the trial was not successful overall, and the company ended the research program. To use this extraordinary responder to further cancer research, MSKCC’s Kravis Center sequenced her entire genome and uncovered more than 19,000 mutations, including the specific mutation that had a synergistic reaction with the study drug.
Solit presented the case to illustrate that “if we could sequence everyone before a trial, then we could know what to give them.” Therefore, the Kravis Center aims to comprehensively profile archived tumor specimens obtained in clinical trials for every type of cancer. The researchers then use the molecular information and correlate it with clinical data, such as a patient’s outcome and response to therapy, to define the molecular driver in all patients, facilitate enrollment of patients into the right clinical trials, and expedite and streamline cancer genomics research to guide cancer treatment.
A hurdle to these goals is the very high cost of genotyping. It is standard of care only in certain types of solid tumors, Solit said, which means that insurance often cannot be billed. Therefore, in 2013, MSKCC instituted MSK-IMPACT™ (Integrated Mutation Profiling of Actionable Cancer Targets), an initiative to detect all known gene mutations in patients with all cancers—both rare and common—at no cost to patients or their insurance. The program now processes about 150 cases per week.
Data from MSK-IMPACT is used to support the development of basket studies, which are phase I clinical trials that offer therapies to patients whose tumors test positive for certain mutations regardless of cancer type or location where the cancer originated. Basket studies can include many more people than disease-specific trials; therefore, they allow for faster enrollment and rapid analysis of results, potentially leading to new therapies more quickly, Solit said.
MSKCC has started to expand the IMPACT program, offering free genotyping to patients worldwide with select rare cancer types. Despite significant challenges, including a lack of much-needed genetic counselors and the difficulties of getting multiple disease teams to work together, Solit said, “At some point, we have to get this out to the broader community. Why wait for the patients to come to us? This is 2017. We have the Internet [and] social media. We have to go out there and find these people.”