Diagnosis of Metastatic Squamous Lung Cancer

Corey Langer, MD:This 70-year-old female presents with shortness of breath and right-sided chest pain of 3 months’ duration, 25-pack-a-day/year smoker for the past 25 years. Chest x-ray, unfortunately, reveals a pathologic fracture in the right fourth rib and a large right-sided pleural effusion. CT scan confirms the presence of the effusion, as well as multiple lytic lesions in the spine and ribs and a spiculated 3-cm mass in the right upper lobe, presumably the primary tumor. Core needle biopsies performed of this mass and pathology show poorly-differentiated squamous cell carcinoma; p63 and CK5- and CK6-positive with abundant cytokeratin. Genetic testing is negative for known driver mutation. PD-L1 testing by IHC shows expression level about 20%, not hitting that 50% cutoff. The patient received palliative radiation to the rib, and then options for systemic treatment were discussed.

For an individual of this sort who presents with metastatic lung cancer, treatment-naïve, they should routinely undergo PD-L1 testing. Based on the KEYNOTE-024 trial, those with PD-L1 expression 50% or higher did far better with a single-agent, pembrolizumab, PD-1 inhibitor compared to standard platinum-based chemotherapy combinations. The response rate was 45% compared to about 28%. We observed a 4.3-month improvement in median and progression-free survival, from 6 months to 10.3 months, and a statically significant improvement in overall survival despite crossover in the control arm to PD-1 inhibition. At 1 year, 70% were alive in the pembrolizumab arm compared to 54% in the chemotherapy arm. Unfortunately, this individual would not have qualified for that clinical trial. The cutoff for entry was expression levels of 50% or higher. In her case, her expression level is 20%. In that group, standard cytotoxic platinum-based chemotherapy is our usual approach. In the modern era, with nanoparticle albumin-bound paclitaxel and carboplatin, I would expect a median survival of, in a good performance status individual, 15 to 20 months potentially. Historically, median survival would have been maybe 10 to 12 months at best.

So, this individual cannot be managed by medical oncology alone. She has a painful rib metastasis, that’s her presenting complaint, and the quickest way to palliate that pain is the judicious use of local radiation to that rib. The vast majority of individuals who receive such treatment will experience pain relief. When it’s given in conjunction with systemic treatment, we’ll often see reossification of the bone, healing of pathologic fracture. And if pain can be controlled, performance status will improve and will actually enable the patient to be better able to tolerate the toxicities of systemic treatment. An interdisciplinary and multidisciplinary approach is absolutely essential when we’re managing patients, even those with metastatic cancer, not just those who have early-stage resected disease or locally advanced non—small cell. And this isn’t necessarily preemptive supportive care; this is absolutely essential symptom-dictated palliation.

Transcript edited for clarity.

March 2017

• A 70-year-old female presents with shortness of breath and right-sided chest pain of 3 months’ duration
• She has a 25-year (1-pack/day) smoking history
• Chest X-ray revealed a pathologic fracture of the right 4th rib and a large right-sided pleural effusion
• CT scan confirmed the presence of a 3 cm spiculated mass in the right upper lobe, moderate right pleural effusion, and multiple lytic lesions in the spine and ribs
• Core needle biopsy of the lung mass was performed
  • Pathology showed poorly differentiated lung squamous cell carcinoma, p63+ and CK5/6+ with abundant cytokeratin
  • Genetic testing was negative for known driver mutations
  • PD-L1 testing by IHC showed expression in 20% of cells
• The patient received palliative radiation therapy to the rib
• Options for systemic therapy are under discussion