Challenges in Treating Squamous NSCLC

Benjamin Levy, MD:Patients with squamous cell lung carcinoma more commonly have comorbidities. These patients generally are more likely to be smokers and may have more comorbidities that may make it tougher to treat—maybe hypertension or coronary artery disease or COPD. And so, we always have to factor in the total patient when we’re treating them. These comorbidities have to be factored in. Patients with squamous cell oftentimes tend to be more symptomatic, tend to have a more pronounced shortness of breath, cough, and even hemoptysis. And in my experience, this has been the case. These patients tend to be a little more symptomatic in terms of their disease presentation and also have those comorbidities that may make it very hard to treat them. So, those are the 2 things that I think differentiate squamous cell clinically from many of my adenocarcinoma patients. Hemoptysis can occur in adenocarcinoma, but I think, at least in my experience, it has occurred more commonly in those patients who have centrally located tumors that are squamous cell carcinoma.

All patients with stage 4 lung cancer, whether it be adenocarcinoma or squamous cell, unfortunately, the goals of therapy are palliative and not curative. But I think the paradigm is shifting. I think when I see patients with squamous cell lung cancer that are stage 4, I always offer a message of hope in the context of what’s being realistic. And I think 5 to 10 years ago, all we had to treat these patients were older chemotherapeutic regimens. We’ve made some strides with some chemotherapy advances, as well as other types of therapies, including immunotherapy. But unfortunately, despite these new advances, the message to the patient is that any treatment that I give them is palliative and not curative. If you look at the data, patients with squamous cell lung cancer who are stage 4 have a median life expectancy anywhere from 12 to 18 months with treatment. But the bar is moving and changing. Given all the new therapeutic advances that we have, those numbers are shifting by the month. So, when patients ask me what my prognosis is or ask me “How many months do I have to live?”, I try to hold on stating a number because every patient is different and we have to individualize treatment decisions. I tell patients they’re not a number, they’re a patient, and everyone is different.

There are a lot of factors to consider now for a patient with advanced stage squamous cell lung cancer that weren’t there in 2013. Of course, we have to factor in how the patient looks, their performance status, the presence of comorbidities, how fit they are, and their willingness to undergo cytotoxic chemotherapy. I think all of those things have to be factored in when we’re making a decision about how to treat these patients. But I think, importantly, what we now know is that we can do PD-L1 testing on a patient with squamous cell. And if they have a tumor proportion square greater than 50%, those patients are candidates for immunotherapy.

So, that’s changed. We used to not factor in PD-L1 testing for patients with squamous cell, but that’s now the standard of care. It’s a very different paradigm these days. But no matter what we’re going to give that patient, we have to factor in those comorbidities, their willingness to undergo therapy, and their understanding that treatment is palliative and not curative. Those are all very important considerations as we move forward.

Transcript edited for clarity.

April 2013

• A 72-year-old female presented to her primary care physician with symptoms of shortness of breath and increased cough.
• The patient has a 40-year (1 pack/day) smoking history.
• Chest X-Ray revealed a right upper lobe opacity.
• CT of the chest and abdomen showed a 3 cm. right upper lobe mass, pleural thickening, and a left adrenal gland nodule.
• She underwent core needle biopsy, the left adrenal mass showed squamous cell carcinoma that was p40+ and p63+.
• PET/CT indicated stage IV squamous cell lung cancer.
• The patient began chemotherapy with carboplatin/nab-paclitaxel.
• CT after 2 cycles of therapy indicated that her tumor burden decreased significantly. At that point the patient reported improvement of her symptoms.
• After 6 cycles the patient had stable disease.

October 2015

• Routine follow up imaging showed a new left upper lobe mass of 2 cm.
• The lung lesion was biopsied and confirmed to be of squamous cell histology.
• Based on multidisciplinary assessment, the new lung lesion was treated with stereotactic radiosurgery.

June 2016

• The patient reported symptoms of coughing and shortness of breath.
• CT showed increased diameter in both lung masses. The adrenal mass remained stable.
• The patient was subsequently started on nivolumab.