A Case of ALK-Rearranged Non-Small Cell Lung Cancer

Lyudmila A. Bazhenova, MD:We have a 59-year-old Caucasian male who presented with symptoms of coughing. He went to see his primary care physician. He’s otherwise healthy, with no significant medical problems. He has a little bit of high blood pressure, which is controlled. He has a little bit of osteoarthritis. He is a former smoker, but he quit 10 years ago. For the workup, it led to a CT scan of the chest, which showed a 6-cm mass in the lower part of the lung and, unfortunately, also revealed fluid in the lung, pleural effusion, and multiple liver metastasis. At that time, of course, cancer was suspected, and the patient was referred for a biopsy. The patient had a bronchoscopic biopsy of the lung mass as well as drainage of the pleural effusion, and, unfortunately, both of them came back as adenocarcinoma.

Following that, the patient had molecular testing as well as immunohistochemical testing performed. He was positive forALKby immunohistochemical testing. He was negative forEGFR,ROS, andBRAFwith next-generation sequencing, and he also had an immunohistochemical stain performed to determine the expression of PD-L1. That was negative as well. He had a PET/CT scan, which showed increased uptake in primary tumor mass as well as the multiple liver masses. And then he had a brain MRI, which was negative for metastatic disease. The patient was tried on therapy with crizotinib, and he responded. He had imaging done at 3 months and imaging done at 6 months, which showed the response, and imaging at 9 months showed a very small increase by 2 mm in 1 of the lung masses.

Unfortunately, because the tumor had moved outside of the chest—it’s involved in both pleural effusion as well as the liver—we are dealing with metastatic, also known as stage 4, lung cancer. So, what that means for us as an oncologist is that we cannot cure this patient; however, we can provide them with improved quality of life as well as prolongation of survival in some cases. And, in this patient, I think the most important thing to point out is that he has anALKfusion gene, and we have a very effective treatment forALKfusion patients.

When the patient was diagnosed, it was August of 2016. At that time, the only choice we had of ALK inhibitors for patients who hadn’t been treated with ALK inhibitors was crizotinib. So, the decision at that time should have been between, “Should we give this patient a platinum-based doublet, which is an approved chemotherapy for this situation?” or, “Should we go ahead and give them a targeted treatment in this situation?” and that was crizotinib. To answer the question, we should know the results of PROFILE 1014 study. The PROFILE 1014 study took patients, who are untreated, with stage 4 lung cancer and randomized them to platinum-based chemotherapy versus crizotinib. And the study showed that crizotinib improved response rate, improved progression-free survival, and more importantly, improved quality of life compared to chemotherapy. So, I think back in August of 2016, crizotinib would be the right choice for this patient.

Transcript edited for clarity.

ALK-Rearranged NSCLC Progressing on Crizotinib

August 2016

• A 59-year-old Caucasian male presented with symptoms of cough and dyspnea
• PMH: hypertension managed on a calcium channel blocker; osteoarthritis
• Former smoker, 10 pack-years
• CT of the chest and abdomen revealed a 6.0 cm spiculated mass in the left lower lobe, a loculated pleural effusion in the right hemithorax, and diffuse liver nodules
• Bronchoscopy and transbronchial lung biopsy revealed a poorly differentiated adenocarcinoma of the lung. Cytopathologic examination of pleural fluid was positive for malignancy
  • Molecular testing:
    • IHC: positive forALKgene rearrangement
    • NGS: negative forEGFR, ROS1, BRAF
    • IHC: PD-L1 expression in 0% of cells
  • PET/CT showed¹⁸F-FDG uptake in the left lung mass, right pleura, and liver
  • Brain MRI, negative for intracranial metastases
• The patient was started on therapy with crizotinib
• Imaging at 3 and 6 months showed continued shrinkage of the lung mass and liver lesions and resolution of pleural metastases
• Imaging at 9 months showed a small increase (2 mm) in the lung mass

June 2017

• After 13 months on crizotinib, the patient reported mild dyspnea and weight loss
• CT of the chest and abdomen showed increased size of 1.5 cm in the pulmonary mass, several new small lesions in the right lower lobe (<1 cm), and 2 left-sided adrenal masses, measuring 3.0 cm and 3.2 cm
• Brain MRI, negative for intracranial metastases