Treatment Options in ALK+ NSCLC

David Spigel, MD: When a patient has anALK-rearranged lung cancer, you still have all the usual options for treating lung cancer. Just to go through them: You have chemotherapy, immunotherapy, and then what we call targeted therapy. So, chemotherapy would not be the best choice for this patient up front, because we have head-to-head studies that have shown the oral agents are better than chemotherapy. And so, that’s a proven strategy, to use an oral agent as opposed to chemotherapy up front. Immunotherapy is still a bit of a wild card. We don’t have head-to-head comparisons.

We know immunotherapy is quite effective in patients with high PD-L1 expression, but if this patient had high PD-L1 expression in anALK-rearranged tumor, we still would push providers to choose a targeted option to address the driving alteration in this cancer as opposed to giving this patient immunotherapy. There’s more that needs to be done to demonstrate the value of immunotherapy in this select patient group, but for now, we think the oral agents are so superior in terms of efficacy and safety that you wouldn’t want to miss that opportunity. It’s a little bit different in lung cancer than it is in melanoma, where we don’t think the same way, but they’re different tumors.

Fortunately, there are a number of therapies that are available for patients withALK-rearranged lung cancer, both in the first- and second-line settings. In the first-line setting, the first drug to come out was crizotinib. It was proved to be better than chemotherapy, and that has remained the standard of care. More recently, we have data from a trial called the ASCEND-4 study that compared a next-generationALKinhibitor, ceritinib, with chemotherapy. It too was superior to chemotherapy, and that has become a new standard in the first-line setting. So, crizotinib is an option, and ceritinib is an option. They both have proved to be better than chemotherapy.

There’s yet another drug, alectinib, which is a next-generation ALK inhibitor. Now, regarding the trial comparing it with chemotherapy, we don’t have those results, but we do have results of alectinib versus crizotinib. We have 2 large randomized trials that have shown superiority for alectinib versus crizotinib. That’s not an approved strategy yet in the first-line setting, but I think it will be very soon. So, that brings 3 agents into the first-line setting: crizotinib, ceritinib, and alectinib. Alectinib has been proved to be better than crizotinib, but we have no data to say that it’s better than ceritinib. I would say right now, in the United States, we certainly have 2 next-generation ALK inhibitors that look to be very effective in the first-line setting, and they would be options for this patient.

Transcript edited with clarity.

• A 62-year-old female never-smoker presented with dyspnea, cough and fatigue.
• Patient has a performance status of 1 due to the decrease in her daily activities.
• Chest X-ray showed multiple bilateral lung nodules.
• PET/CT showed left adrenal metastases.
• Brain MRI was negative.
• Bronchoscopy was performed with a fine needle aspirate biopsy.
• Pathology results showed moderately differentiated adenocarcinoma.
• Molecular testing showed ALK-rearrangement.
• Patient was started on ceritinib.