Chemotherapy Is Still Standard for Squamous NSCLC

Benjamin Levy, MD:Despite this whole immunotherapy story that has been so exciting for all of us, and surprisingly showed a benefit in treatment-naïve patients, immunotherapy is restricted to those patients with a tumor proportion score greater than 50%—and in the literature, that’s only about 25% of all patients. And I will tell you, in my practice, it has been less than that. So, it’s more common for me to consider chemotherapy than it is for me to consider immunotherapy for patients with stage 4 squamous cell. And chemotherapy remains a cornerstone; it is going to be more commonly used. And what we know about chemotherapy is, it does work in squamous cell lung cancer patients. It can improve quality of life, it can extend life, and it can improve cough and shortness of breath, and this has been fleshed out in the literature. Even with carboplatin/Abraxane, there have been some nice data that it at least maintains quality of life while going through chemotherapy.

So, while I think it’s very exciting to talk about immunotherapy strategy frontline, and if you have me back here in 1 year, I may be telling you something different, given how fast things are moving. Right now, in 2017, for those patients with a tumor proportion score less than 50%, chemotherapy remains the cornerstone for patients with squamous cell. And unfortunately, squamous cell has not shared the same advances that adenocarcinoma has. We can’t parse out squamous cell into these unique genetic subsets and wed them to targeted therapies. What we know now is just PD-L1—positive greater than 50% immunotherapy, PD-L1–positive less than 50%, then off of a clinical trial, these patients should be getting chemotherapy. And the message to our patient and the message from me to my patient with squamous cell is, “It works. It can’t cure you. The gold therapy is palliative, but it can extend your life and it can improve your quality of life.”

I think we have good head-to-head data now comparing carboplatin/nab-paclitaxel versus carboplatin/paclitaxel in a very large study. And the bottom line from this study was in the intention-to-treat analysis. Now, this study included both adenocarcinomas and squamous cells. In the intention-to-treat analysis, there was no difference in overall survival. However, when they looked at the subset analysis from the squamous cell, there was an improvement in response rate with carboplatin/Abraxane versus carboplatin/paclitaxel. And I think the response rate’s important for our patients with squamous cell who come in with so many symptoms. So, there’s an improvement in response rate.

There were also some interesting nuances from this trial. At least in those patients who were enrolled in North America—this was a global trial—there was an overall survival advantage for patients who got carboplatin/Abraxane versus carboplatin/paclitaxel. And then, in those patients over the age of 70, for reasons that I can’t explain, there was also a benefit in overall survival with carboplatin/Abraxane versus carboplatin/paclitaxel. Now, I would always temper any retrospective analyses, but it does give some hints of activity in certain patient populations. So, based on the response rate advantage, based on the fact that many of our patients come in with so many symptoms, I think this is a very reasonable option for our patients. The other issue is toxicity, and there’s differences in toxicity with carboplatin/Abraxane versus carboplatin/paclitaxel. Carboplatin/Abraxane tends to have less neuropathy, which is important, and so that’s something to consider when thinking about how to tailor treatment for your patients with squamous cell.

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.