A Case of ALK+ NSCLC

David Spigel, MD: This is a 62-year-old, otherwise healthy woman who presents with evidence of lung nodules on a routine chest X-ray. Additional imaging included PET scanning, which found evidence of lesions in the adrenal gland. This patient underwent bronchoscopy with fine needle aspiration, which identified adenocarcinoma, and additional molecular testing identified anALK-rearrangement. This patient was felt to be a good candidate for therapy, with an ECOG performance status of 1, and is looking at a standard option here, up front, as her first line of therapy.

This patient is typical of someone we would see, either in the hospital as a consult or as a new patient in our clinic. There are a couple of things to point out in the workup of these patients. So, this particular patient had a bronchoscopy and fine needle aspiration. That is very common. What’s uncommon about this scenario is to get theALKresults: FNAs, unfortunately, frequently don’t provide enough information to getALKtesting performed at a lot of community hospitals. And so, my only teaching point for this is that you don’t stop there. If you just found out this woman had lung cancer, but you didn’t have enough testing to doALK, I would say that this patient needs a second biopsy because you wouldn’t want to deny her a chance to get an effective oral first-line therapy. The other thing I’d mention in the workup here is brain imaging.ALK-rearranged lung cancers are frequently associated with metastases to the brain. It’s a part of normal lung cancer workup for anybody with advanced disease, but this patient especially needs brain imaging, ideally in the form of an MRI. PET scanning will not adequately address that.

This is a patient whom we would consider giving up-front oral tyrosine kinase inhibitor therapy. This is not a patient we would give chemotherapy to. We used to, but now we know better, that an oral ALK inhibitor is going to outperform chemotherapy in the first-line setting. We now have 2 large randomized trials that have proved that. And so, for this patient, we would offer them that therapy.

We get excited when we identify these alterations in the initial evaluation of patients, primarily because the therapies are so effective and it’s so gratifying to be able to give somebody an effective therapy up front. The prevalence ofALK-rearrangements is low enough that you don’t see this routinely, certainly not in the community setting, where you’re seeing a lot of different kinds of malignancies. About 4% to 6% of patients will have this kind of lung cancer. We know that patients will generally fit a certain phenotype or clinical picture, so they tend to be nonsmokers and a little bit younger. But that doesn’t mean you can’t have an 85-year-old patient with anALK-rearranged lung cancer or even a smoker. I’ve had that very patient in my clinic.

These patients tend to do very well, and that’s because the therapies are so effective. These patients tend to be at the upper end of the bell curve, so to speak, in terms of responding to therapy— having a prolonged progression-free survival, so living without their cancer growing, and overall survival. They also do well with chemotherapy as a later line of care. One thing I will say, though, is that patients withALK-rearranged lung cancers have aggressive cancer, not to be dismissed as an indolent situation where you don’t have to do anything quickly. These cancers can grow quickly, can progress quickly, and can be life-threatening for patients in a very quick way. So, identifying the cancer, finding the right therapy, and getting it started are really paramount.

Transcript edited for 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.