Treatment Algorithm for Squamous NSCLC

Benjamin Levy, MD:So, in 2017, for a patient who is squamous cell and who is a former heavy smoker, I generally don’t perform molecular testing on these patients. I think what we know is that patients with squamous cell who are never-smokers—and we have some of those, they’re rare—those patients we should routinely be offering EGFR- and ALK-rearranged testing on, to identify. But for patients who are heavy or former smokers, and the data are a little bit unclear, I don’t routinely offer molecular testing for those patients. I think what we know about squamous cell is that the genetic alterations that are relevant in squamous cell are different than the genetic alterations that are relevant in adenocarcinoma. Adenocarcinoma is a very nice pie of mutually exclusive drive mutations, and we don’t necessarily see that same pie in squamous cell. There are potential actionable mutations in squamous cell. One isFGFR1amplifications, one isDDR2, and the other isPI3kinase mutations. But these mutations, unfortunately at this time in 2017, aren’t actionable. And most of the studies that have looked at these types of genotype-directed therapies toward those alterations have been unsuccessful. So, because of that, unless they had a remote history of smoking or they’re a never-smoker—and in that case, I will do EGFR and ALK—I don’t routinely recommend molecular testing for squamous cell.

But I want the message to be clear here. Molecular testing and PD-L1 testing are 2 different things. And just because we’re not routinely doing molecular testing on squamous cell lung cancers, we still need to do PD-L1 testing. PD-L1 testing is an IHC. It’s a protein test. And that has to be done on every advanced squamous cell cancer that comes through the door. So, I think there has been a lot of confusion in the community that PD-L1 testing is molecular testing. It’s not; it’s an IHC test that needs to be done, even if you’re not going to be doing molecular testing on your squamous cell lung cancers.

It’s important, in this day and age where tissue is so precious, that we really start considering core needle biopsies for all of our patients with lung cancer or suspected lung cancer. Fine needle aspirates can be fine in some instances, but given the need for more and more tissue to perform molecular testing and PD-L1 testing, I try to make every effort to get a core biopsy for patients with lung cancer. And that doesn’t mean it happens all the time. I think there are lesions that we can see and identify that are just more easily accessible by bronchoscopy with an FNA.

But we have to really be mindful of tissue procurement and tissue stewardship. And in this day and age, it’s not enough to call lung cancer “non—small cell lung cancer.” We have to identify the histology. But more importantly, we have to do the genomic alteration identification, as well as the PD-L1. So, I would make a call to be very mindful. I don’t want to say every patient has to have a core needle biopsy, but make a call to the community and the academic folks to be mindful when you’re considering tissue procurement to make sure that every effort is made to get as much tissue as possible so that these tests can be done so treatment decisions can be individualized.

So, the algorithm for treatment has changed dramatically for advanced squamous cell lung cancer in the past few years, not only in terms of chemotherapy, but in terms of immunotherapy. I’ll skip to the exciting news first. For patients that have a PD-L1 tumor proportion score of greater than 50% now, these patients should be offered immunotherapy with a checkpoint inhibitor, with pembrolizumab or Keytruda every 3 weeks. And this is based on seminal work comparing pembrolizumab to chemotherapy that was recently published in theNew England Journal of Medicineshowing that those patients that had a tumor proportion score greater than 50%—and these were patients that had both adenocarcinoma and squamous cell—derived an improvement in response rates, improvements in progression-free survival. But most importantly, improvement in overall survival with the use of pembrolizumab compared to chemotherapy. And because of that, every patient who now walks through the door who has an advanced squamous cell lung cancer needs to have PD-L1 testing. If it’s less than 50%, I generally don’t offer immunotherapy. That’s not to say that these patients may not derive a benefit from an immunotherapy up front—and I’m talking about just in treatment-naïve patients. Less than 50%, that’s where I think chemotherapy plays a role.

And when we look at chemotherapeutic strategies for squamous cell lung cancer, it really is a story of competing standards. Of course, there’s carboplatin/paclitaxel—that’s an oldie, but a goodie. It’s one that’s been used for years. There has obviously been cisplatin/gemcitabine, that’s a histology-woven story from the Scagliotti data. And then, more recently, carboplatin/Abraxane, which has really been a regimen that I’ve been very comfortable with for the past few years, and we’ve got good data. In a head-to-head trial comparing carboplatin/Abraxane to carboplatin/paclitaxel—very large study—at least in the subset analysis for the squamous cell patients from that study, there was a benefit in response rate for carboplatin/Abraxane, or carboplatin/nab-paclitaxel.

My clinical experience has mirrored what the data would suggest. These patients do derive a benefit. They have an improvement in their response rates, they have an improvement in their quality of life, and based on that, I’ve been comfortable using carboplatin/Abraxane. We don’t have a lot of head-to-head trials between these 3 regimens: gemcitabine/platinum, carboplatin/paclitaxel, and carboplatin/Abraxane. They’re all reasonable to consider. In my experience, I’ve been more comfortable using carboplatin/Abraxane. Not to say I haven’t used carboplatin/gemcitabine in the past, I have, but I think all 3 are reasonable options and are supported by literature.

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.