Treatment of a Patient With ALK-Positive Non-Small Cell Lung Cancer

Corey Langer, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, presents a case of oligoprogressive ALK-positive metastatic non-small cell lung cancer to illustrate the role of surgery in patients experiencing isolated progression during targeted therapy.

The case demonstrates how multidisciplinary evaluation and bilateral adrenalectomy allowed continuation of alectinib despite adrenal progression, resulting in more than 8 years of progression-free survival. It also underscores the importance of repeat molecular testing in patients with clinical features suggestive of an oncogenic driver, as identification of an ALK rearrangement fundamentally changed the patient's treatment course.

Transcript: 

Hello, my name is Corey Langer, I'm the director of thoracic oncology at the Abramson Cancer Center and professor of medicine, Perelman School of Medicine, University of Pennsylvania, in Philadelphia. And it's my privilege to discuss the role of surgical resection, what we call locally ablative therapy, in the setting of oligoprogression, limited sites of progression, in a patient with an oncogenic driver, specifically an ALK fusion, on an appropriate TKI. 

This is a patient in my practice, a 54-year-old semi-retired attorney who presented in 2017 with progressive shortness of breath and recent diagnosis of bilateral lower-extremity deep vein thromboses. CAT scan in February of [20]16 actually showed a right lower-lobe pulmonary embolism and a 38 mm by 32 mm mass in the medial left lower-lobe with multiple small surrounding nodules, a separate lesion in the right upper-lobe and fairly extensive mediastinal and hilar adenopathy. CAT scan of the abdomen and pelvis disclosed metastasis to the liver and both adrenals, and PET at that time, confirmed FDG-avid disease in the left lung as well as right lung nodules, supraclavicular mediastinal, and hilar node as well as bilateral adrenal lesions and multiple bone metastases. So, extremely aggressive disease, multi-organ, stage 4, non-small cell [lung cancer]. 

Molecular testing at that time, including ALK FISH, was consistently negative for actionable mutations or fusions, so the patient was started off at an outside institution on pemetrexed, carboplatin, and bevacizumab which was one of the standard regimens of that era and initially she sustained a partial response, but unfortunately after 6 months, while on maintenance therapy with bevacizumab and pemetrexed, she developed disease progression in both the liver and adrenals. The latter was treated with radiofrequency ablation, so she had some transient response.

At this point she re-presented to us and we retested her tissue. She had been a never-smoker, she was relatively young, disease-type histology was adenocarcinoma, and female. That sort of phenotype when it comes to lung cancer, that type of patient, will often have tumors with actionable oncogenic drivers. And in fact, when we did retest her tissue, we found a somewhat obscure ALK rearrangement. She was started on the standard treatment of that era, crizotinib, in August of 2016 [and] initially responded but it was very brief and by January of 2017, she had disease progression in both the liver and adrenals. 

At that time, alectinib was initiated and she had essentially a complete remission in the liver and the lungs and the nodes in her bones, with increasing sclerotic change, with the exception of adrenals which both became large and necrotic. The big question at this point was what to do? Should we switch therapies? Should we go back to chemotherapy? Should we use an alternative TKI or was an ablative approach, specifically surgery in her situation feasible? Since we were talking about both adrenals, could this patient survive a bilateral adrenalectomy? 

It took considerable discussion, multiple conversations with our dedicated surgical oncologist, but in fact, particularly after pointing out how well alectinib was working outside the adrenals, we did persuade our surgical oncologist to go ahead and perform bilateral adrenalectomy. She was placed on appropriate hormonal replacements since she was now in surgically-induced adrenal insufficiency, had a relatively uncomplicated post-op course and I am happy and proud to say that 8 years later, and counting, she remains on alectinib with absolutely no evidence of disease progression. We image her at this point initially every 3 months now every 4 to 6 months [and] we include brain imaging, in light of her ALK fusion with high propensity for CNS metastasis, but there has been absolutely no evidence of disease progression either within the CNS or extracranial. 

She's tolerating alectinib quite well, her only complications being mild constipation and occasional muscle cramps. She's leading essentially normal life. If you were to look at her, you would never know she had this cancer history. The only concession to her diagnosis is the ongoing need to stay on alectinib indefinitely and she is taking full dose at 600 mg twice a day, and as I said, tolerating it fairly well.