Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the activity of larotrectinib (Vitrakvi) in patients with 

 fusion—positive non–small cell lung cancer.

At the 2019 European Lung Cancer Conference, Drilon reported data from the larotrectinib series on the outcomes of the 11 patients with NSCLC who harbor 

 fusions. Investigators found that there was a high response rate to therapy with some deep responses. There was a 71% objective response rate, among which there was 1 complete response. Moreover, every patient had disease reduction.

At the interim analysis, the median duration of response was not reached. Most patients who received larotrectinib for their 

 fusion—positive lung cancers remain on therapy, says Drilon. The longest reported time on therapy is approximately 2.5 years, he adds.

The last aspect of the trial that was featured at the meeting was the intracranial activity of larotrectinib. Three out of 11 patients had brain metastases on the trial. Though some have questioned the activity of TRK inhibitors in the CNS, investigators noted that patients had disease regression both extracranially and intracranially, says Drilon.

Videos

Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, discusses the activity of larotrectinib (Vitrakvi) in patients with TRK fusion–positive non–small cell lung cancer.

Dr. Drilon on Activity of Larotrectinib in TRK Fusion-Positive NSCLC

Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, discusses rare drivers in non—small cell lung cancer (NSCLC).

There are several other emerging biomarkers in addition to 

 fusions, for example, are found in up to 2% of patients with NSCLC. Although older multikinase inhibitors showed modest activity, there were issues with tolerability.

Since then, more selective RET inhibitors have been introduced into the clinic. These include BLU-667 and LOXO-292, both of which show high tolerability and response rates ranging from 50% up to 70%. In September 2018, LOXO-292 received a breakthrough therapy designation from the FDA for the treatment of patients with 

 fusion—positive NSCLC. The agent also holds designations for advanced 

 fusions or rearrangements, which are found at a high frequency in some rare cancers, such as salivary cancers or breast cancers, but also at a lower frequency across other solid tumors, like lung cancers, says Drilon. Two first-generation TRK inhibitors are now in development: entrectinib and larotrectinib (Vitrakvi), updates on both of these agents were presented at the 2018 ESMO Congress. Across any solid tumor that harbors an 

 fusion, investigators reported a response rate of about 57% with entrectinib, while updated data with larotrectinib showed a response rate of about 80%.

Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, discusses rare drivers in non–small cell lung cancer (NSCLC).

Dr. Drilon on Rare Drivers in NSCLC

Alexander E. Drilon, MD, medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, discusses the adoption of next-generation sequencing (NGS) in lung cancer.

NGS is used more commonly now than ever before, explains Drilon; however, certain challenges remain. For example, some physicians are not familiar with the best NGS tests that are out there, of which there are many. Moreover, each test can be vastly differ from another. There are 2 major strategies for NGS, he says: amplicon-based testing and hybrid capture. At MSK, physicians use a hybrid capture-based NGS, which is most likely better at detecting a wider variety of actionable alterations.

A couple of NGS tests are authorized or approved by the FDA. For example, the test physicians use at MSK, known as MSK-IMPACT, has FDA authorization. There is also the FoundationOne assay, which can also be used as a companion diagnostic to select appropriate patients for a particular targeted therapy, says Drilon. In selecting an NGS assay, physicians have to be cautious of whether or not the test can detect fusions in addition to regular mutations and whether the assay can detect copy number changes and any other alternation outside the scope of what is found in lung cancer.

Dr. Drilon Discusses the Adoption of NGS in Lung Cancer

Alexander E. Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the combination of tepotinib and gefitinib (Iressa) in patients with 

-mutant non—small cell lung cancer (NSCLC).

There are 2 types of MET activation in lung cancer, explains Drilon. The cancer can be dependent on MET alone or the cancer can acquire a dependence on MET in the case of an 

 mutation. A patient who receives a first- or second-generation EGFR TKI can develop 

 amplification. A substantial amount of patients who receive osimertinib (Tagrisso), a third-generation inhibitor, also develop 

Therefore, several programs have investigated the combination of an EGFR and MET inhibitor. The combination of tepotinib and gefitinib has shown activity in a select group of patients, says Drilon. As was the case with de-novo 

 amplification, the higher the amplification, the higher the response. The median progression-free survival in patients with 

 amplification was 21.2 months with the combination versus 4.2 months with chemotherapy.

Alexander E. Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the combination of tepotinib and gefitinib (Iressa) in patients with MET-positive EGFR-mutant non–small cell lung cancer (NSCLC).

Alexander E. Drilon, MD

Articles

Dr. Drilon on Activity of Larotrectinib in TRK Fusion-Positive NSCLC

Dr. Drilon on Rare Drivers in NSCLC

Dr. Drilon Discusses the Adoption of NGS in Lung Cancer

Dr. Drilon on Tepotinib and Gefitinib in MET+ EGFR-Mutant NSCLC