Further Optimizing the Treatment of Non-Driver NSCLC

Mark Socinski, MD:As I previously mentioned, I typically continue immunotherapy for up to a couple of years. That’s assuming the patient’s benefiting from it and not having undue toxicity. If I think they’re not benefiting from it, what do we do third-line? I think in a patient like this, the third-line option, in my mind, would be docetaxel. And typically, when I use docetaxel, I combine it with ramucirumab. We know from the REVEL trial that the addition of ramucirumab to docetaxel improved response rates, progression-free survival, as well as overall survival. And assuming that the patient didn’t have any contraindications to an anti-VEGF agent like ramucirumab, I would use that agent in this particular setting. So, that would be my third-line choice.

So, as I mentioned, I view this patient as having treatable but not curable disease. What’s going to happen in the next 3 to 5 years? Well, there are some efforts looking at, are there clearly oncogenic driver pathways in squamous carcinomas that can be targeted? There’s a very important trial ongoing in the United States, called the Lung-MAP trial, that’s run by the Southwestern Oncology Group. That is looking at squamous patients in the second-line setting, trying to define oncogenic drivers and then trying to match them with targeted therapy. So, it’s an important trial. Have we seen any successes to date in squamous? No, but we must remain hopeful that we will uncover something.

The other issue that we talked about is the role of immunotherapy. And I think that we’ve just kind of scratched the surface with immunotherapy with the anti—PD-1 and anti–PD-L1 agents. We’re beginning to see some early data with combination immunotherapy strategies, particularly combining the PD-1, PD-L1 access with CTLA4 combinations. The data are still very, very early. But I think, particularly in squamous, that there may be hope and enthusiasm for various immunotherapy combinations that may yield a greater benefit. Some of the early data do suggest that, but we haven’t seen a lot of the data. And there are certainly lots of potential agents that could be combined in this particular setting to benefit the patient.

So, I’m more optimistic about the immunologic approach than I am about the targeted approach in squamous patients. But I think we need to keep an open mind and keep enrolling on to important clinical trials.

Transcript edited for clarity.

• A 72-year old male presented with dyspnea, weight loss, chronic cough, fatigue, and back pain
• PMH: current non-smoker for the past 10 years with 40-year (1-pack/day) smoking history, COPD, controlled on LABA/LAMA/ICS; hyperlipidemia controlled on atorvastatin
• Chest CT scan showed a 3.5-cm nodule in the upper lobe of the left lung
• MRI of the brain revealed lesions in the left cerebellum and left frontal lobe
• 99mTc bone scan showed increased uptake in the L1 vertebra and eighth rib
• ECOG PS=1
• Pathologic diagnosis of biopsy under bronchoscopy was squamous cell carcinoma
• IHC: PD-L1 expression in 0% of cells
• Patient was started on gemcitabine/cisplatin
• Brain metastases treated with stereotactic radiotherapy
• At 6 months, patient reported worsening fatigue
• Follow up MRI scan showed no evidence of new brain metastases
• CT scan showed new lesions in the right lung and liver
• Patient was started on atezolizumab; ICS medication for COPD was discontinued
• Patient reported decreased appetite, which resolved following implementation of self-management techniques