The Picture Is Finally Changing in Squamous NSCLC

Published: Friday, Apr 22, 2016
Dr. Benjamin P. Levy

Benjamin P. Levy, MD

Treatment options for patients with squamous non–small cell lung cancer (NSCLC) are expanding rapidly yet the field is still lagging in targeted therapies and curative strategies, according to leading researchers who participated in a recent OncLive Peer Exchange® roundtable.

Additional research is needed not only to define new combination regimens that would benefit patients but also to identify biomarkers that could be targeted in clinical trials, the experts said during the program, entitled “Treating Advanced Squamous Non–Small Cell Lung Cancer.”

“Until recently, little progress had been made in the area of squamous non–small cell lung cancer. Now, with the excitement of recent positive trials and new drugs approved, there are increasing options for patients and the hope of improved outcomes, particularly after failure of chemotherapy,” said Benjamin Levy, MD, who served as moderator for the session.

In less than 18 months, the FDA has approved these drugs for squamous NSCLC: the EGFR inhibitors necitumumab (Portrazza) and afatinib (Gilotrif), the PD-1–targeting immunotherapies nivolumab (Opdivo) and pembrolizumab (Keytruda), and the antiangiogenic antibody ramucirumab (Cyramza).

“That’s unprecedented,” said panel member Paul K. Paik, MD, in reference to the pace of approvals. “And yet, if we look at lung adenocarcinoma as the cousin or the sister or brother [of squamous NSCLC], they’re far better off. And they’re far better off, by and large, because targeted therapy is reality for them.”

Defining the Subtype

Squamous cell carcinoma, which comprises approximately 25% to 30% of all lung cancer, is the second-largest histological subtype of NSCLC after adenocarcinoma, according to the American Cancer Society.

Yet distinguishing between squamous and nonsquamous subtypes—and deciding which patients should undergo molecular testing—is not always straightforward, panelists indicated.

To diagnose squamous cell NSCLC, both immunohistochemistry findings and the patient’s clinical presentation are equally important, Levy said.

Edward S. Kim, MD, FACP, said many patients with squamous NSCLC treated at the regionally based community healthcare system where he practices present with a central mass that is causing bronchial constriction.

These patients are often older, in their 70s and 80s, and are active smokers or have recently quit.

Paik agreed with that clinical profile and noted that offering treatment to these patients is a priority. “The main concern for these patients are the symptoms that they’re having and our need to really palliate these things as soon as we can,” he said.

Looking for targetable genetic mutations has been a limited strategy until recently. Squamous NSCLC is a genetically complex disease, Levy said, and the state of knowledge of relevant genetic alterations is not advanced.

However, the National Comprehensive Cancer Network (NCCN) now supports limited testing for EGFR mutations and ALK rearrangements in never- smokers with squamous histology, Paik said, as some patients derive benefit from relevant inhibitors. Kim’s advice to the general oncologist is that patients who are never-smokers or have a light smoking history and an atypical presentation should be tested.

Chemotherapy

Chemotherapy doublets have been a backbone of first-line treatment for patients with squamous NSCLC, but these regimens typically consisted of a platinum agent combined with gemcitabine or a taxane until a large phase III study that compared carboplatin with either nab-paclitaxel (Abraxane) or solvent-based paclitaxel.1

Dr. Edward Kim from Carolinas HealthCare System

Edward Kim, MD

In all, 1052 patients with untreated stage III-IV disease including 450 participants with squamous NSCLC were randomized to either treatment regimen. Among the squamous population, the nab-paclitaxel regimen demonstrated a 41% overall response rate (ORR) compared with a 24% ORR for participants who had taken the solvent- based paclitaxel combination.

There was a nonsignificant advantage in overall survival (OS) and a more favorable adverse event profile with carboplatin/nab-paclitaxel, Levy said. He said the regimen resulted in lower rates of neuropathy, myalgia, and arthralgia but a higher incidence of neutropenia, anemia, and thrombocytopenia. Another advantage of the nab-paclitaxel regimen is that premedicating with steroids is not needed, Levy said.


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