Considerations at Progression of Squamous NSCLC

Benjamin Levy, MD:This happens a lot. Patients have drank the immunotherapy Kool-Aid, which is good. There are a lot of advertisements out there, and they’re very excited about it. But I tell a lot of other physicians, our job is to be excited about this, but to also temper the enthusiasm of immunotherapy at times because immunotherapy only works currently in roughly 20% of patients. So, what about a patient who comes in whose PD-L1 proportions, tumor proportion score is less than 50% and they’re getting chemotherapy? Oftentimes, I have to convince them that chemotherapy is going to work better than immunotherapy, and that’s important. Chemotherapy is right for that patient. But many patients, once they’re on chemotherapy, even if they’re doing well, have heard so much about immunotherapy that they want the immunotherapeutic strategy. And one of my jobs, first of all, is to be their advocate. And being their advocate means keeping them on the chemotherapy, if they’re tolerating it, as best I can.

Immunotherapy, I tell them, only works in 20% of the patients, and if you’re already on chemotherapy and you’re doing well, then I think it’s important that you at least complete the 4 to 6 cycles that are warranted in your case. And this is, actually, the real world. We encounter this issue a lot with patients who either don’t want chemotherapy up front or are on chemotherapy and want to jump off and go to immunotherapy. And I think it’s incumbent upon physicians to make sure we relay the realistic message of immunotherapy, which is that it works, but it works in a subset of patients. And if you’re deriving a benefit from chemotherapy, you stick with chemotherapy until it’s not working or you’re not tolerating it. Then, we can have that discussion with immunotherapy. Of course, this is for patients with tumor proportion scores less than 50%. I’ve had many patients come to me saying they don’t want chemotherapy, they want immunotherapy, in which we know their PD-L1 score is 0%. And they say that they still want immunotherapy. You have to convince them, and you have to back it up with the science and the data, that chemotherapy is really your best option for longevity, tumor control, and quality of life.

I think it’s really important that every time we’re thinking of a therapeutic switch, we really assess the patient’s performance status and really come to terms with whether a patient can truly derive a benefit from any drug we give. So, performance status is important in making decisions. Patients with performance statuses of 3—and we have many of them who, unfortunately, are getting chemotherapy who then progress and have a rapid decline—I generally don’t offer those patients any drug. Whether immunotherapy would benefit a patient with an ECOG performance status of 3 is unclear, but I think we have to be realistic about what the goals are when patients are either starting treatment, have never received treatment before, or are progressing on a current line of treatment, and really look carefully at their performance status, understand what the true goals are here, and what will really be meaningful for patients.

I had a patient recently who, unfortunately, had progressed on carboplatin/Abraxane. Her tumor had grown, she had a rapid decline with disease growth everywhere, and unfortunately had supplemental oxygen, was in a wheelchair, and said, “I want immunotherapy.” And this is a tough one because you want every patient to try to get to see immunotherapy at some point along their treatment continuum. But that has to be tempered with, whether if there’s any benefit to giving a patient like that any type of strategy. So, I would make sure that you really are assessing the patient in terms of what their performance status is before making a decision with any drug.

I don’t think we know if chemotherapy elicits dynamic changes within the tumor that would make patients more eligible or more likely to respond to immunotherapy second-line. I think this is theoretical and based on some preclinical work that immunotherapy may work better after chemotherapy because chemotherapy elicits these changes that can upregulate neoepitopes, and that may make the immunotherapy better able to harness the immune system to turn against that which is perceived to be more foreign based on that upregulation of the neoepitopes. I don’t know if we know that yet. I don’t know if we know that clinically. I think that, in my mind, it’s pretty straightforward—patients with tumor proportion scores less than 50% at this point.

Now things may change. So, if you come back 6 months from now, it may be very different. But tumor proportion scores less than 50%, they should get chemotherapy, and outside of a clinical trial, there’s no argument there. And then, if they’re doing well, they stay on chemotherapy. As soon as their tumor’s grown or they’re not tolerating it, they get immunotherapy. And I say that matches in the context that things are changing dramatically. And in 6 months, it may be different. Maybe every patient is getting immunotherapy with chemotherapy irrespective of their tumor proportion score, I don’t know. But as it stands now, we really diverge our treatment plans based on that PD-L1 tumor proportion score.

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.