Therapy for Progression of Squamous NSCLC

Benjamin Levy, MD:So, it’s always important to have a multidisciplinary assessment for patients with lung cancer, and this case highlights the challenges. This is a patient who derived the benefit from chemotherapy, had stable disease for close to a year, and who then had a new lesion. I think it’s reasonable for a patient that’s fit and has a new lesion, or a new mass, in the setting of overall stable disease otherwise to consider biopsying that lesion. One, it may be a different cancer. Two, you may be able to figure out the genetic underpinnings if it is a different cancer. And so, patients that are fit and who have derived a benefit from chemotherapy who’ve had stable disease for over a year, I think it’s reasonable to identify what’s growing.

And that was what was done in this case. Once the biopsy was performed and we identified that this was squamous cell, this is where the real critical assessment begins. Do we necessarily consider that progression, given that all other sites of disease in the body are stable? Does that mean we pull the trigger and move to a second type of drug or immunotherapy? Or do we consider it a local ablative therapy? And I would make an argument for a fit patient who has had stable disease and other sites of disease for over a year, who has one new spot, I think it’s reasonable to consider local therapy.

But just this highlights how important multidisciplinary conferences and tumor boards are to have these discussions, to have the surgeon in the room, to have the radiation oncologist in the room, to have the medical oncologist in the room, and to have the pathologist and the radiologist. Lung cancer has gotten so complex and we’ve got so many new therapeutic advances, not only in the systemic realm, but in the local ablative realm, in the surgery realm. Everyone needs to come together in either a shared virtual space or physical space to discuss these patients, and the patients deserve it. I think maybe 5 to 10 years ago, this patient would have gotten chemotherapy second-line, and I’m not sure this patient at that point, with just one growing spot, warrants systemic treatment that may cause more side effects. So, I encourage all patients that any nuance of delivery of care, especially as they progress, and especially in these cases of oligometastatic disease, we really consider them to be candidates to the discussion on a multi-tumor board, a multidisciplinary tumor board.

So, the treatment paradigm has dramatically been altered in the past 2 to 3 years for squamous cell and for all non—small cell lung cancer. I think 5 years ago, we would have offered docetaxel or another cytotoxic chemotherapy. We now have very good data, multiple phase III trials, showing that immunotherapy is superior to chemotherapy for patients that are chemorefractory. And I guess the first question is, well, when do we make that decision? When do we decide to institute immunotherapy or any second-line drug for that matter? I think this treatment decision has to be individualized. You have to look at the patient and ask yourself, “What’s the overall burden of disease doing in that patient, and how symptomatic are they?” Every patient is different. And I think it takes a real critical assessment to understand when it’s time. But if I see a patient who has worsening symptoms and I have radiographic evidence that the cancer is growing, it’s time for a therapeutic switch. And that therapeutic switch off of a clinical trial is usually immunotherapy, for most patients.

Not all patients are candidates for immunotherapy, and we need to remember that. Patients with autoimmune diseases, patients on steroids, they may not be the best candidates. For many of our patients, however, we now have 3 approved drugs in the chemorefractory setting for squamous cell. First is nivolumab. And nivolumab has come around first and certainly shown an improvement in overall survival compared to docetaxel. Second is pembrolizumab. It also showed a benefit over docetaxel. And then finally, there’s atezolizumab, which most recently showed a benefit over docetaxel in terms of overall survival.

So, we have an embarrassment of riches; we have 3 drugs. Two are PD-1 drugs: pembrolizumab and nivolumab. The other is a PD-L1 drug, which is atezolizumab. All 3 are approved. I get a lot of questions from community doctors, and from other physicians, asking me which one is better. We have no direct head-to-head comparison between these. I think all of them work very well. All of them can be used. With the exception of pembrolizumab, which still requires a PD-L1 greater than 1%, not 50%, in the second line, both nivolumab and atezolizumab don’t require PD-L1 testing.

PD-L1 testing now is going to be done up front anyway. So, you’re going to have that information up front. If they are greater than 1% up front, of course they’re going to get chemotherapy. But then, they can be candidates for immunotherapy; either pembrolizumab, nivolumab, or atezolizumab in the second line. If it’s 0% up front, of course, they’re going to get chemotherapy. But in that case, pembrolizumab can’t be used. You can give atezolizumab (Tecentriq) or nivolumab (Opdivo). So, it’s very confusing. But there are 3 drugs in the second line. Atezolizumab and nivolumab require no PD-L1 testing, and pembrolizumab still requires a PD-L1 testing greater than 1%, which is different than the 50% needed up front to give that drug.

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.