Alexander Drilon, MD, is chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses a study exploring entrectinib in patients with 

-positive, advanced or metastatic non—small cell lung cancer (NSCLC) during an interview at the IASLC 18th World Conference on Lung Cancer in Yokohama, Japan.

 arrangements occur in about 1% to 2% of lung cancers and are highly actionable drivers, Drilon explains. Moreover, entrectinib is a multikinase inhibitor with activity against 

. Data from a pooled phase I/II experience show that, in patients with 

positive NSCLC, by investigator assessment, the objective response rate was 78.1% with entrectinib, and the median progression-free survival was 29.6 months.

Updated data from the IASLC meeting show that there may be better central nervous system efficacy with entrectinib compared with crizotinib. Additionally, preclinical data show that entrectinib is a more potent inhibitor than crizotinib. 

Videos

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses a study exploring entrectinib in patients with ROS1-positive, advanced or metastatic non-small cell lung cancer (NSCLC) during an interview at the IASLC 18th World Conference on Lung Cancer in Yokohama, Japan.

Dr. Drilon on Entrectinib in Patients With ROS1-Positive NSCLC

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses immunotherapy in patients with lung cancer.

Not every patient is going to benefit from immunotherapy, explains Drilon. Data have recently been discovered that the likelihood of response to single-agent immune checkpoint inhibitors in EGFR-mutant and ALK-rearranged lung cancers is relatively low.

These low response rates could be because the tumors that harbor a driver may be more naïve and possibly less visible to the immune system, states Drilon. In clinical trials, the same level of response is not being seen in the patients who have a more substantial smoking history and who don’t have EGFR, ALK, or high PD-L1 staining.

Dr. Drilon on Immunotherapy in Lung Cancer

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses NTRK rearrangement in patients with lung cancer.

NTRK rearrangements are recurrent gene fusions that are found in a rare minority of patients with lung cancer, explains Drilon. However, looking across other solid tumors, they can be found in head and neck cancer, sarcomas, and breast cancer.

According to Drilon, the interesting thing about TRK fusions, is that they are very actionable in terms of targeted therapy. There are 2 different targeted agents, entrectinib and LOXO-101, that are in phase II testing for any patients who have solid tumors with NTRK rearrangement. Both drugs have achieved dramatic responses, regardless of histology in earlier phase I studies.

Dr. Drilon on NTRK Rearrangement in Lung Cancer

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses RET rearrangements for patients with non–small cell lung cancer (NSCLC). 

Beyond EGFR, ALK, and ROS1, there are a number of genomic subsets that have been of interest, particularly RET rearrangements, explains Drilon. RET rearrangements are fusions that are similar to ROS1, and occur in about 1% to 2% of NSCLC. 

In 2016, there were 3 phase II studies, which demonstrated the response rate was anywhere from 15% to 50%, depending on the trial. The lesson there, according to Drilon, is that researchers are not quite seeing the same level of responses that are being seen with ALK and ROS1.

Dr. Drilon on RET Rearrangements in NSCLC

Alexander Drilon, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses two studies investigating entrectinib in patients with advanced solid tumors.

Combined results were recently presented from the ALKA-372-001 study, which explored intermittent and continuous dosing of entrectinib, and the STARTRK-1 study, which looked at continuous dosing of the agent. In a safety analysis of 119 patients, entrectinib was found to be very well tolerated, Drilon says.

The majority of adverse events were grade 1/2 and included fatigue, changes in taste, and paresthesia. One of the longest responders enrolled on the study has been on treatment for 2 years and 3 months, Drilon adds.

Alexander Drilon, MD

Articles

Dr. Drilon on Entrectinib in Patients With ROS1-Positive NSCLC

Dr. Drilon on Immunotherapy in Lung Cancer

Dr. Drilon on NTRK Rearrangement in Lung Cancer

Dr. Drilon on RET Rearrangements in NSCLC

Dr. Drilon on Entrectinib in Patients With Advanced Solid Tumors