Breakthrough Approval Accelerates Precision Medicine

Yesterday, the FDA approved larotrectinib for treatment of solid tumors that have an NTRK gene fusion. This approval represents an important shift towards treating cancers based on their tumor genetics independent of their organ of origin. It is a view into the future where in addition to talking about breast cancer or lung cancer, clinicians will increasingly be talking about the gene drivers of the cancer for selection of therapies that cross traditional organ-defined disease.

 Larotrectinib (commercial name, Vitrakvi) is a breakthrough for cancer patients because of the high clinical efficacy. Clinical trial response rates in cancers with NTRK gene fusions were 75%. To put that in perspective, for non-small cell lung cancer the response rate to chemotherapy is only about 20-30%. In addition, larotrectinib is one of the few cancer drugs that was tested for use in pediatric cancers in parallel with adult cancers, enabling it to be an option for children.

 One of the stories of larotrectinib’s success is the story of Connor Pearcy. Born with a tumor below his right knee, Connor had chemotherapy starting at 7 weeks old. Unfortunately, his tumor did not shrink, and after 5 years of various therapies and surgery, the family had run out of options. Then, his doctor found that his cancer was NTRK positive and he was eligible for the larotrectinib clinical trial. Just a few weeks into kindergarten, Connor started treatment. After 2 months, the MRI showed an 80% reduction in the tumor and 4 months later, the tumor was undetectable by MRI.

 Momentum is building in approvals for precision medicine therapies with larotrectinib as the 2nd therapy recently approved as a “pan cancer” therapy for treating patients whose cancer shows a specific genetic variant or signature. Merck’s Keytruda was the first, approved in 2017 for patients with microsatellite instability (MSI) positive cancer independent of tumor type. While Keytruda was already approved as an immunotherapy and widely used, larotrectinib is the first drug approved only as a pan-cancer therapy based on clinical trials integrating genomic tests.

 I recently re-read the story of Gleevec approval, one of the first oncology therapies based on a gene fusion. As was the protocol 20 years ago, Gleevec clinical trials were organized by cancer organ type and on cancers where the targeted genetic event was very common—it was too hard to find patients for trials any other way. But today, with the cost of sequencing decreasing, genetic biomarkers have become an integral part of drug development. Yet we still need to make more progress in ensuring access to genetic testing for patients—it is estimated that fewer than 5% of tumors today are sequenced, a number that must be increased to capitalize on the promise of precision medicine.

 One way that will happen is through the approval of drugs like this one. While the sequencing for the clinical trials for larotrectinib approval were performed in centralized laboratories, we are excited to partner with LOXO on a decentralized companion diagnostic. This future class III FDA-approved diagnostic will enable genetic testing for NTRK fusions across the world, putting genetic testing in the hands of more clinicians and the potential of a cure to more patients like Connor.