Real-World Selection and Use of IO Therapy in Metastatic NSCLC

In light of clinical data and real-world experience, Jason Porter, MD, considers how he would best select patients with non–small cell lung cancer for IO therapy.


Jason Porter, MD: The FDA approved cemiplimab, along with platinum double chemotherapy, in early November 2022. It’s a very exciting time. Cemiplimab is the only immune checkpoint inhibitor, in addition to pembrolizumab, that’s combined with chemotherapy as a first-line treatment option for patients with metastatic non–small cell lung cancer. We now have 2 anti–PD-L1 therapies indicated in that space. Nivolumab and ipilimumab are indicated, but that’s a combination as opposed to a monotherapy immunotherapy, along with chemotherapy.

It’s very exciting to have cemiplimab as a treatment option in this space. In my clinical practice, I’ve used cemiplimab in combination with chemotherapy. I see efficacy, safety, and tolerability. That’s encouraging for my patients and me. I haven’t experienced many adverse events. I’ve used cemiplimab as a monotherapy and in combination. Patients seem to tolerate it pretty well. I’m monitoring it closely because immune checkpoint inhibitor adverse effects can come anytime after the patient has been treated. Luckily, my patients have tolerated it well with minimal adverse reactions. Some [adverse events] that I’ve seen in the clinic include pruritus, which we knew about from the clinical trial EMPOWER-Lung 3. I haven’t seen anything that was unexpected or any new safety signals in my patients. For the most part, they’ve been able to stay on therapy. I haven’t had to use steroids for any immune-mediated adverse effects for patients on cemiplimab. I know it’s possible. I’m monitoring them closely, but I’ve been very fortunate with my patients so far.

The combination of cemiplimab plus chemotherapy is appropriate when patients have PD-L1 expression of less than 50%. Technically, cemiplimab monotherapy is indicated if the patient’s PD-L1 is greater than or equal to 50%, but sometimes patients have clinical symptoms of disease. Many times in our clinical practice we add the chemotherapy for rapid response. What we saw in the EMPOWER-Lung 3 trial was that even where patients’ PD-L1 expressions were very high, the response or time to response in some instances was as fast, if not faster, than [it was in] patients who received chemotherapy. For a patient who has a very high PD-L1 expression level, I’m not likely to add chemotherapy. I’m more likely to use monotherapy. But for patients 1 to 49 years old or those who have symptoms of disease, and also for patients who have liver metastases, I’m more likely to include chemotherapy.

Some patients have clinical comorbidities that make them not good candidates for platinum double chemotherapy. Severe neuropathy from preexisting diabetes is 1 of those times when I try to avoid chemotherapy. Also, [when a patient has] renal dysfunction that’s not going to tolerate platinum chemotherapy very well, that’s another time when I avoid the platinum double chemotherapy and am more likely to use an immune checkpoint inhibitor monotherapy.

When making treatment selection for metastatic non–small cell lung cancer, whether squamous or not, we need to get deep genomic profiling with a tissue as well as liquid in most cases, so we can rule out actionable alterations. When there are none, the PD-L1 level becomes very important. For PD-L1 expressions that are very high, we can use an immune checkpoint inhibitor monotherapy. Or we can use an I/O [immuno-oncology] combination, such as nivolumab-ipilimumab. Pembrolizumab, atezolizumab, and cemiplimab are all indicated for PD-L1–high expressing tumors, squamous and nonsquamous, as monotherapies.

When the patients have a disease burden that’s high, causing symptoms such as pain worsening, shortness of breath, worsening cough, or hemoptysis, we’re usually going to add chemotherapy to those. Pembrolizumab plus chemotherapy and cemiplimab plus chemotherapy are both indicated in the first line for patients who have metastatic non–small cell lung cancer, who need a platinum doublet chemotherapy in addition to an immune checkpoint inhibitor. Doing so will help us debulk disease and often help us address symptoms that the patient may be experiencing from their disease. For patients who have comorbidities that make them not good candidates for platinum doublet chemotherapy, sticking with an immune checkpoint inhibitor monotherapy or combination is the way to go.

Transcript edited for clarity.

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