First-Line Treatment Options for Metastatic Squamous Cell NSCLC

Comprehensive insight on the first-line treatment armamentarium available to patients diagnosed with metastatic squamous cell non–small cell lung cancer.


Jason Porter, MD: My treatment decision for this patient was to put him on cemiplimab, an immune checkpoint inhibitor, plus platinum doublet chemotherapy. My decision was swayed by his metastatic disease to the liver, also the relatively large size of his mass, and the pain that he was experiencing in his right lower back, which may have been related to metastatic disease in his liver. He had symptoms, including worsening dyspnea, all of which [INAUDIBLE] maybe want a pretty rapid response. Now we know patients who have PD-L1 expressions that are very high, greater than or equal to 50%, typically respond very well to immune checkpoint inhibitor monotherapy such as cemiplimab or pembrolizumab, also atezolizumab. But for this patient, his PD-L1 expression level is only 30%, so I felt like chemotherapy was definitely indicated as a part of his initial treatment plan and approach. That’s how I made my initial treatment decision for him.

Also, if he had brain metastases at the time of diagnosis, the only change that I would’ve made to my approach is to give him brain-directed therapy up front. If it was an isolated brain metastasis, either surgery or a gamma knife, or stereotactic radiosurgery [SRS] for his brain. And then, I would proceed with the systemic therapy as planned. If he didn’t have liver involvement, I may do brain resection, gamma knife, or SRS for the brain and then go for a more curative approach with chemotherapy and concurrent radiation followed by immune checkpoint inhibitor or surgical resection after neoadjuvant therapy for oligometastatic disease. But we know with liver involvement, this was not the case for him. So, if he had brain involvement and it was isolated with no other metastatic disease, a more definitive approach may have been implicated.

Other first-line treatment options for a patient in a similar clinical scenario include CheckMate 9LA, where we give 2 cycles of platinum doublet chemotherapy in addition to nivolumab and ipilimumab, followed by ipilimumab and nivolumab maintenance for those patients. That clinical trial, CheckMate 9LA, was a large phase 3 clinical trial. It included over 700 patients who were treated according to the regimen that I just stated, and they were treated and compared with patients who had 4 cycles of platinum doublet chemotherapy. In the CheckMate 9LA trial, we saw overall survival, and our data analysis is out to 3 years now, and there’s more than 27% of those patients still alive who were treated with platinum doublet chemotherapy followed by immune checkpoint inhibitor maintenance. And there was platinum doublet chemotherapy with immune checkpoint inhibitor nivolumab and ipilimumab, followed by nivolumab-ipilimumab maintenance. So there’s improvement in overall survival, and also progression-free survival regardless of PD-L1 expression.

In CheckMate 9LA, the patients did not have to have PD-L1 expression. They were stratified by PD-L1 expression as less than 1% or greater than equal to 1%, and also by their histology, squamous vs nonsquamous. We didn’t see quite as good a survival for the patients who had the nonsquamous disease, but we did see good improvement in overall survival for patients with or without brain metastases. Now, in the overall survival for patients with brain metastases, we saw 35%. For patients without brain metastases, overall survival at 2 years was 39%. So with or without brain metastases, for those patients who had treated and stable brain metastases.

Another treatment option for patients who have squamous cell carcinoma as metastatic is derived from the KEYNOTE-407 trial. Those patients were treated with pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel. That was compared with platinum doublet chemotherapy alone, without the pembrolizumab. The overall survival of those patients at 5 years is now 18.4% for those patients who are treated with pembrolizumab plus platinum doublet chemotherapy, vs less than 10% at 9.7% for the patients treated with platinum doublet chemotherapy. So, 2 treatment options in addition to cemiplimab plus the chemotherapy, which I chose for this patient, include the CheckMate 9LA regimen and KEYNOTE-407 regimen.

Transcript edited for clarity.

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