I’m Dr Benjamin Levy; I’m the director of thoracic medical oncology at Mount Sinai health systems and Mount Sinai Hospital. I’ll be talking today about chemotherapeutic and targeted strategies for squamous cell lung cancer. Squamous cell tends to be a challenging disease and difficult to treat, and often times can carry a lot of symptoms with it, and patients can experience those symptoms. And certainly we need to be proactive in first diagnosing this as well as treating it.
In terms of chemotherapy strategies, I think it’s a theme of competing standards. There is not one right regimen, but there are several. Of course there’s carboplatin + paclitaxel. This is a regimen that we know, from the ECOG 1594 study, was at least as good as cisplatin-base containing regimens, and better tolerated. That study included both adenocarcinoma and squamous cell. Certainly carboplatin + paclitaxel—an oldie but a goodie—is one that could be considered for squamous cell.
And then more recently, we have the histology-directed therapy story from the Scagliati data comparing cisplatin + gemcitabine to cisplatin + pemetrexed in a very large study—over 1700 patients—and think what we found in that study is in the subset analysis for the squamous cell patients, patients did a little bit better with cisplatin + gemcitabine in terms of overall survival than they did with cisplatin + pemetrexed. And because of that, I think cisplatin or carboplatin with gemcitabine is a reasonable regimen as well for squamous cell.
Of course, more recently, we have data that adding necitumumab to cisplatin + gemcitabine, when compared to cisplatin + gemcitabine alone, provided a survival advantage and a progression-free survival advantage. And because of that, I think if you are considering platinum gemcitabine, you should consider adding necitumumab, given the survival advantage that we saw.
And then finally, carboplatin + nab-paclitaxel (Abraxane) is another chemotherapeutic regimen that is highly active in squamous cell patients. We do have a head-to-head trial between carboplatin and nab-paclitaxel vs carboplatin + paclitaxel. And in the subset analysis from the squamous cell patients, there was a very high response rate—41%—in those patients who had squamous cell who received carboplatin + Abraxane.
So what do I do? In most of my patients, I do use carboplatin + Abraxane. I will admit that I’m putting many of my patients in a clinical trial with this regimen. The regimen is well-tolerated, and certainly has been found to be efficacious in studies. The targeted therapy paradigm that we’ve witnessed in adenocarcinomas, we have not yet seen in the squamous cell population. So when we start talking about targeted therapies for squamous cell, as of today, there is not an FDA-approved targeted therapy for squamous cell, and that’s challenging. For better or for worse, squamous cell has not shared the same advances with targeted therapies that adenocarcinomas have had.
We now know, for adenocarcinomas, there are these nice pie graphs with mutually exclusive driver mutations, which we can wed to targeted therapies. We have EGFR, ALK, BRAF, HER-2, ROS, and RET, that all exist in the adenocarcinoma population. But unfortunately, for squamous cell, we haven’t seen that. And there has been ongoing work: in 2012, there was The Cancer Genome Atlas (TCGA) that did try to search for genomic underpinnings of squamous cell, and did find some relevant genetic alterations.
I think the ones that continually come to the surface are FGFR1 and PI 3-kinase; these are certainly potentially targetable. I can tell you that there are multiple studies ongoing right now looking at some targeted therapies for these mutations, and in the response rates haven’t been what we’ve seen in the in the EGFR and ALK patients that get TKI therapy. I would just make a pitch: given that we really don’t have targeted therapies approved for squamous cell, there is a study, the Lung-MAP—the SWOG study—that is specifically addressing this, looking at targeted therapies for patients who have advanced squamous cell lung carcinoma who have progressed on a platinum doublet. And then, if they have a particular target, they can be eligible for a targeted therapy and that is looking at an FGFR1 inhibitor as well as a PI-3 kinase-directed therapy. And I would say that any patient who progresses on platinum chemotherapy—if that trial is open—should go on that study.
So, a lot of unanswered questions, certainly: chemotherapy strategies are here to stay upfront for now, for advance squamous cell carcinoma of the lung. And hopefully, in the next 5 to 10 years, we’ll begin to see approval of targeted therapies for this very challenging disease.