The Case for Alectinib in ALK-Positive NSCLC

At the Great Debates & Updates in Lung Cancer meeting in New York, New York, Ticiana Leal, MD, Winship Cancer Institute, Emory University, Atlanta, Georgia, debated in favor of alectinib over lorlatinib when considering treatment options for patients with ALK-positive non-small cell lung cancer (NSCLC).

Transcript:

My name is Dr Ticiana Leal, I'm an Associate Professor and Director of the Thoracic Medical Oncology Program at the Winship Cancer Institute of Emory University and today's day 1 of Great Debates & Updates in Lung Cancer in New York. We've had a great meeting so far with lots of updates in EGFR, updates in immunotherapy in lung cancer and today Dr [Misako] Nagasaka [MD, University of California, Irvine, California] and I actually had a debate in ALK [-positive] non-small cell lung cancer. The debate was alectinib versus lorlatinib. And I was tasked with the mission of debating in favor of alectinib in patients with ALK [-positive] non-small cell lung cancer. It was a great debate. The highlights of my debate were the significant improvements in PFS, OS, intracranial PFS, overall response rate, and certainly safety of alectinib in front-line for patients with ALK [-positive] non-small cell lung cancer so, I defended the paradigm of using alectinib up front followed by potentially lorlatinib in second-line and then clinical trials or chemotherapy in third-line and beyond.

This is an area of active investigation and I think we also talked about the benefits of alectinib that have been established in now several trials both in the Western population as well as in the Asian population. We have now the results of 5-year updates of alectinib in non-small cell lung cancer so certainly establishing the role of alectinib in patients with ALK [-positive] non-small cell lung cancer. I think one of the great advantages too is now we have the results, at least the press release from the ALINA trial. We've had a lot of advances in the adjuvant space, in the neoadjuvant space in non-small cell lung cancer, we've seen the approval and now the overall survival of EGFR-targeted therapy in non-small cell lung cancer in the adjuvant space. Now we saw the press release of the ALINA trial, which was a trial that investigated the use of alectinib versus chemotherapy in patients with resected non-small cell lung cancer with an ALK fusion and we saw that in that press release there is an improvement in disease-free survival for the use of alectinib versus chemotherapy. We're waiting to see those results, but that may change how we use alectinib and now we're moving alectinib now to the curative setting. I think that's very promising and brings a lot of hope for our patients with non-small cell lung cancer.

I think one of the things that's very clear is alectinib has really demonstrated and changed the way that we treated patients with ALK [-positive] non-small cell lung cancer. It was one of our first approvals in front-line with the second generation ALK TKIs, so we've been using alectinib for a long time. And so, it first came to market as the frontline strategy as a second generation ALK TKI that was well-tolerated, so I've been using it for a long time, have a lot of familiarity with prescribing, with managing side effects, with counseling patients on the risks and benefits of using alectinib. Certainly, I frequently use alectinib in front-line.

Now, there are certain situations that I would consider lorlatinib use in frontline as well. Based on the data, I think the intracranial PFS of alectinib is very robust, but certainly again with the caveats of cross-trial comparisons, the intracranial PFS of lorlatinib so far looks remarkably good and so for patients with high burden of metastatic disease with CNS involvement, I do counsel patients about the use of lorlatinib, but I have an informed decision-making discussion with my patients about risks and benefits of each approach. Their opinion and their decision on it in the end trumps our decision of what they want to try. These are therapies that they use long-term, these are therapies that hopefully they'll use for years so certainly, managing side effects, and I think the safety of alectinib is superior, also factors into the decision-making as well.

Source:

Leal, T. Debate: alectinib vs lorlatinib in ALK positive- Alectinib. Presented at Great Debates & Updates in Lung Cancer; September 21-September 23; New York, NY.