Advanced Squamous Non-Small Cell Lung Cancer: Case 1 - Episode 1
Corey Langer, MD:This is an 81-year-old gentleman who presents to his physician with cough, hemoptysis, and fatigue requiring increasing rest during the course of the day. Past medical history is reasonably unremarkable. He has a history of hypercholesterolemia, which is controlled on a statin, and hypertension, which is well controlled on a calcium channel blocker. So, this gentleman has no history of smoking. He’s quite active. He continues to play golf several times a week, he drives, and he’s fully independent and maintains all his normal activities of daily living. Chest x-ray and CT show a cystic mass in the left upper lobe, as well as lymphadenopathy in the left hilum and both mediastinal nodes. PET/CT confirms these findings, showing fairly marked FDG uptake in the lung mass and in lymph nodes. Bronchoscopy and transbronchial lung biopsy are performed, and path confirms grade 3 squamous cell carcinoma of the lung. Genetic testing, in light of his never-smoking history, is performed, and this is completely negative, with no evidence of an oncogenic driver. PD-L1 testing by IHC shows expression in 65% of cells. The individual was started on treatment with pembrolizumab, with follow-up imaging at 3 months showing stable disease.
After about 5 months on immunotherapy, unfortunately, the patient was hospitalized with a seizure. At the same time, he reports increasing fatigue and cough over the preceding month. CT confirms enlargement of the primary mass in the left upper lobe. Brain MRI confirms multiple small intracranial metastases. He is started on whole brain radiation. Immunotherapy is discontinued, and the patient is actually started on a 2-drug chemotherapy combination: carboplatin/nab-paclitaxel and nanoparticle albumin-bound paclitaxel.
So, this gentleman presents with locally advanced squamous cell carcinoma of the lung. Technically, this individual has stage 3B disease; bilateral mediastinal nodes would confirm N3 disease. The primary tumor presumably is at least a T1 or T2. Historically, we would usually treat such an individual with concurrent chemoradiationa platinum-based regimen—either weekly paclitaxel/carboplatin or etoposide cisplatin combined with 6 to 7 weeks of full dose RT (radiation therapy), a minimum dose of 60 gray. We can see cure rates in selected individuals approaching 20% to 25% in that cohort now. There are some individuals, for one reason or another, who are not appropriate for radiation because the field may be too large, there may be additional nuances in a case such as this, or there may be satellite lesions or contralateral intrapulmonary metastases that make full-dose curative chemoradiation inappropriate. If we assume that to be the case here, then the choice of treatment, pembrolizumab—based on the level of PD-L1 expression—is quite reasonable and certainly would be my first choice, assuming we had ruled out a curative approach with chemoradiation.
At this point, I think PD-L1 testing is standard, but clearly, in metastatic or stage 4 disease or in individuals who have recurrent disease, we can debate whether it should be standard or not in stage 3 or stage 3B nonsmall cell. But an individual with noncurable disease, who has the expression levels of 50% or higher, is well served by frontline checkpoint blockade by immune modulator, in this case, pembrolizumab, which has clearly shown a survival advantage compared to standard chemotherapy in this setting.
Now, it’s intriguing. This gentleman has squamous cell carcinoma, which almost always, but not always, is associated with the smoking history. And yet, he was a never-smoker. Had he been a heavy smoker, now with squamous cell, I’m not so sure I would have ordered molecular testing. Next-generation sequencing takes 2, 3, or 4 weeks minimum to turn around. We would end up delaying our intervention based on this waiting period, and the likelihood of actually harboring a mutation in the setting of the smoker probably would be less than 1% to 2%. But in a never-smoker, regardless of histology, I think it is reasonable to obtain mutation testing or molecular testing and look for actionable molecular aberration. I would guestimate that the rate of mutations in that group, the never-smokers, even with squamous cell would be on the order of about 10% to 15%. So, it’s a perfectly reasonable option.
Transcript edited for clarity.