COMMENTARY

Antibody-Drug Conjugates, Targeted Therapies Lead Lung Cancer Data

Mark G. Kris, MD

Disclosures

June 01, 2016

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Hello. I'm Mark Kris from Memorial Sloan Kettering, and I'm speaking to you today to give you a brief update on what to expect at the upcoming meeting of the American Society of Clinical Oncology (ASCO) in Chicago, starting next week. I've had the opportunity to review the program for abstracts dealing with thoracic malignancies, and I would like to highlight the range of information that you are going to see presented there. I'll hopefully whet your appetite and encourage you to either show up in person if you're attending the meeting or listen to the online presentations when they're available.

This year you're going to hear a huge range of information. Some of it is extremely interesting and exciting. The first thing that particularly excites me are two presentations on antibody-drug conjugates: one using an antibody targeting an antigen in small cell lung cancer,[1] and one in non–small cell lung cancer[2] with a chemotherapeutic agent attached.

What I see in these presentations is a new way to take an old friend—and that is chemotherapy—and deliver it to those patients who have a target. We've all been very heartened by the benefit that people with breast cancer have had by using ado-trastuzumab emtansine (TDM-1), where the emtansine chemotherapy agent is conjugated to trastuzumab, and tiny amounts of drug—amounts that could not lead to any serious cytotoxicity-type symptoms or other chemotherapy-related symptoms—are brought right to the tumor with the antibody and seem to be making a huge difference. We're seeing that kind of benefit now coming to the lung cancer area, in both small cell and non–small cell, and that is going to be very, very exciting.

We're also going to hear new developments in targeted therapies. I think the highlight is going to be the clinical trial[3] already reported in the financial world comparing alectinib with crizotinib. It was only inevitable that when we had more agents for specific targets and saw that the activity of the agents and their side-effect profiles were different, that there would be randomized trials. This trial compared alectinib, an ALK kinase inhibitor that also has activity against ROS1, against crizotinib, another ALK kinase inhibitor with activity against ROS1. What has already been reported was a significant improvement in progression-free survival at the endpoint of the trial.

We've already seen this type of trial done in renal cell cancer, where multiple kinase inhibitors are available, and we've now seen them come to lung. As clinicians, we have a difficult situation now that we have multiple drugs to choose from, both in the EGFR and ALK space. Which is the best drug to recommend for each treatment setting, particularly at initial therapy? This trial in the ALK space is one of the first ones to have widespread discussion and presentation. It's going to be one that is going to make us think and hopefully give us some guidance for how to proceed.

There are also new agents coming up for the targets that we are already facing. We already have brigatinib for ALK-positive cancer,[4] and lorlatinib for both ROS1- and ALK-positive lung cancers.[5] I think both of those presentations will be interesting.

Plucked from the lung session by the organizers of the meeting is an abstract reporting the nationwide experience using crizotinib for patients with MET exon14 splice variants.[6] Two years ago at ASCO, you heard about the use of MET kinase inhibitors in patients who have amplification of the MET gene. Here you see very clear improvements with crizotinib, a drug we know and trust in patients who have MET mutations. Not MET amplification, not MET protein expression, but MET mutations. This is going to be at one of the major clinical science symposia. This is a very important abstract mainly because it allows you to immediately treat patients with this aberration with a drug that we all have available.

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