Atezolizumab's Role in Treating Non-Driver NSCLC

Mark Socinski, MD:At the time of disease progression, this patient was treated with atezolizumab. The basis of that, or the rationale for that, is really the results of the OAK trial. Atezolizumab was compared with docetaxel in the second-line setting in patients who had received prior platinum-based doublets. It did show an overall survival advantage that was significant, I think both statistically as well as clinically significant in this patient population.

The benefit of atezolizumab seemed to be independent of PD-L1 status. We know this patient was PD-L1—negative. In that group in the OAK trial, in the initial analysis of the original 850 patients, there was clear benefit in those patients that were PD-L1–negative. So, that would be the rationale for this particular patient. Obviously, there are 2 other drugs in this space: nivolumab (Opdivo) and pembrolizumab (Keytruda). Nivolumab would have been a reasonable choice. Pembrolizumab would not have been indicated because pembrolizumab is indicted only in patients who are PD-L1–positive, and in this case, he was negative.

One of the clinical features that we see with immunotherapy is that patients who are smokers tend to get greater benefit than nonsmokers with immunotherapy. As I mentioned earlier, squamous histology and smoking are very tightly linked. Almost all patients with squamous carcinoma have a history of smoking. So, they’re kind of the best candidates for immunotherapy. And in this case, in the OAK trial, there was clear benefit. Of course, now we’re getting into some subset analyses, which it’s hard to draw too many firm conclusions from the subsets. But I do think the data with atezolizumab, as well as other agents, do clearly support the use of immunotherapy. And my personal bias, in looking at the literature, is they may actually get a little more benefit because of this link to smoking from immunotherapy.

The patient was started on atezolizumab, and the paradigm with immunotherapy is that we continue it, assuming the patient has some evidence of clinical benefit, has some evidence of disease control, and is not having undue side effects. One of the controversies today is, how long do you continue it or how frequently may you have to administer? Many of the clinical trials were designed to give it for 2 years and then arbitrarily stop it at that point if the patient’s disease was still controlled.

So, in this patient, unless there was a reason to stop it—and the reasons to stop it would either be the cancer is growing through it or they’re having some undue side effect—I would continue and up to 2 years. And then we have that discussion with patients at 2 years, what should we do afterwards, and there are really no clear data as to whether or not one should continue beyond 2 years. Or if the cancer is well controlled, can you give the patient a break? So, I think that’s one of the areas of controversy where we don’t really have clear data.

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