Role of Molecular Profiling in Squamous NSCLC

Benjamin P. Levy, MD:If they’re never-smokers, squamous cell patients need the same exact workup that an adenocarcinoma patient has. At the very minimum, they need to test forEGFR,ALK,ROS, andBRAF. Those are the approved biomarkers, or actionable mutations, but I would argue that you should do comprehensive genomic profiling. At my institution, we do a 300-gene panel that can pick up point mutations and rearrangements. You also need to do PD-L1 testing. Remember, the frontline trial for pembrolizumab included squamous cell patients. For every never-smoker patient with squamous cell cancer, the diagnostic and molecular workup should be identical to that of a patient who has adenocarcinoma.

I tell patients with advanced stage squamous cell disease that they’re not curable, but they’re certainly treatable. I try to steer away from survival times, but if we look at the survival times for a squamous cell patient with advanced stage disease, survival times can range anywhere from 12 to 16 months. We’re learning more and more about the role of immunotherapy and this concept of the tail of the curve being pushed up. We know that there’s a subset of patients who receive immunotherapy, with adenocarcinoma or squamous cell carcinoma, who are living for a long time. In fact, there’s a recent updated analysis that shows that the 5-year survival rate with single-agent nivolumab in a highly pretreated group of patients from the phase I experience is 12% to 13%, which is much higher than we usually see. Although numerical survival times can be disappointing, we know that there are outliers and that patients are living for a very long time.

Transcript edited for clarity.

Case: A 53-Year-Old Woman with mNSCLC Rapid Progression

• A 53-year-old woman presents with a lump in her left deltoid and no other signs or symptoms
  • PMH: insignificant, currently on no medications, no smoking history
• Chest X-ray showed a 5-cm soft tissue mass
• Biopsy showed advanced squamous cell carcinoma, TTF-1-
  • Molecular testing negative for known actionable mutations
• PET CT revealed a liver lesion and adrenal mass
• Brain MRI showed no evidence of CNS metastasis
• Staging: T2aN3M1b
• 22C3 antibody testing; PD-L1 TPS, 0%
• The patient is started on cisplatin/gemcitabine
• Imaging at 3 months shows widespread progression with new and enlarging lesions including a significant increase in her soft tissue and lymph node disease, collapse of her right lower lobe and new liver lesions