Herbst Highlights the Implications of the FDA Approval of Adjuvant Pembrolizumab in NSCLC


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Roy S. Herbst, MD, PhD, discussed the data that supported the FDA approval of adjuvant pembrolizumab in patients with non–small cell lung cancer, highlighted the implications of the approval for the paradigm, and outlined further research opportunities.

Roy S. Herbst, MD, PhD

Roy S. Herbst, MD, PhD

Although atezolizumab (Tecentriq) previously received FDA approval for the adjuvant treatment of patients with non–small cell lung cancer (NSCLC), pembrolizumab (Keytruda) represents another immunotherapy option that is now approved for use in this setting—one that is indicated for a broader range of patients, according to Roy S. Herbst, MD, PhD.

On January 26, 2023, the FDA approved pembrolizumab for use as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC, based on findings from the phase 3 KEYNOTE-091 trial,(NCT02504372).1 Data from the trial showed that the median investigator-assessed disease-free survival (DFS) was 58.7 months (95% CI, 39.2-not reached [NR]) with adjuvant pembrolizumab vs 34.9 months (95% CI, 28.6-NR) with adjuvant chemotherapy (HR, 0.73; 95% CI, 0.60-0.89).

“This is a broader approval than [that of adjuvant atezolizumab],” explained Herbst, who is an ensign professor of medicine in Medical Oncology and professor of Pharmacology, the director of the Center for Thoracic Cancers, the deputy director of clinical affairs, and assistant dean for Translational Research at Yale School of Medicine. “There are other [immunotherapy] drugs approved [in NSCLC], which speaks to the importance of this class of drug. However, this is a broader approval because it includes stage IB [T2a ≥4 cm]; it [is] also [indicated] regardless of PD-L1 status.”

In the interview with OncLive®, Herbst, who is also the chief of Medical Oncology and associate cancer center director of Translational Science at Yale Cancer Center, Smilow Cancer Hospital, in New Haven, CT, discussed the data that supported the FDA approval of adjuvant pembrolizumab in patients with NSCLC, highlighted the implications of the approval for the paradigm, and outlined further research opportunities.

OncLive®: What is the significance of the FDA approval of adjuvant pembrolizumab in NSCLC?

Herbst: It is exciting to see pembrolizumab—the first drug approved in the frontline setting for NSCLC—now being approved [for use] in the adjuvant setting. It is [now indicated] following the resection of stage IB, II, and IIIA [disease]. The KEYNOTE-091 trial, also referred to as the PEARLS trial, showed that there was a 27% [reduction in the risk of recurrence or death] in patients who also had adjuvant chemotherapy, [regardless of PD-L1 status].

This is important because it gives us a new standard of care [SOC]. Atezolizumab [Tecentriq] had already been approved [for use] in this setting, but with some limitations based on PD-L1 status and [disease] stage. However, [the pembrolizumab approval] goes from stage IB, II, and IIIA, regardless of PD-L1 status.

[Pembrolizumab] is [an agent] that we’ll begin to use in the clinic. It’s important because we want to do the best we can for patients. We want to remove the cancer to prevent it from spreading to the other lung, the liver, the bone, or the brain. By using these types of agents, these early data show that [we may be able to achieve] this. Now, we wait for survival data [to read out] from this trial.

What were the efficacy and safety data reported with this approach?

The efficacy [achieved with this approach] is quite clear. This is a big benefit—more of a benefit than one sees with adjuvant chemotherapy— [and] with fewer toxicities. There are certain significant immune-related toxicities one needs to be aware of, including inflammation in the lung, the colon, the thyroid, and other organs, and we [need to] watch for that. That being said, this [approach] adds something else to the armamentarium.

Having been treating patients with lung cancer for over 25 years, the fact that we’re bringing our best drugs—this being immunotherapy—to the earliest stages and improving DFS [is encouraging], and hopefully at some point we’ll show that this affects overall survival. Keeping the disease from going to vital organs is important for patients.

What we are constantly trying to do is bring better drugs to patients. This is the sixth approval for pembrolizumab in NSCLC, and I’ve been fortunate to be involved with some of the [efforts associated with the] earlier ones. Certainly, this is something that we’ll want to take advantage of in our clinics.

Is there anything else that should be known about the safety profile of the agent in this setting? Are there any patients for whom you would not recommend its use?

I don’t believe the safety profile is any different from what we’re used to with immunotherapy, such as inflammation or itises; most [effects] are low grade and can be treated with moderate steroids or even stopping the drug for a certain period of time. In a small percentage of patients, you can see significant inflammation in the lung, liver, or thyroid, and that requires a little more therapy.

However, the only patients I would avoid [adjuvant pembrolizumab] in [are those] who [have] a preexisting autoimmune condition. If someone has lupus, [for example,] or another autoimmune condition, we would avoid [pembrolizumab]. However, [in general], that's been the SOC for how we already work with immunotherapy.

Following this approval, what other unmet needs require additional developments and research?

Certainly, we will want to do even better. [In the future,] we will want to understand [whether there] are other combinations of drugs that might be more effective [in the adjuvant setting]. The HR [for DFS] was 0.73 [in KEYNOTE-091]. Could it be better if we find out why some patients aren’t benefiting as much? That will involve biomarkers, and we’re now in an era where we can measure circulating tumor cells or circulating tumor DNA [to] understand who might need more treatment vs less. That is research that will occur in the future.

Many of these therapies are moving to the neoadjuvant setting. We already use these [therapies] after chemoradiation, so there are many indications now for using immunotherapy. Pembrolizumab was one of the first agents approved in the frontline setting of lung cancer; that was huge—that we were using it in the frontline setting. Now, the fact that we are using it in the adjuvant setting, even earlier, is very exciting.

The goal to eradicate this disease is to find the cancers earlier with screening. Many of these patients probably were smokers, and smokers do fit into the screening guidelines. We [need to] screen patients to find the cancers earlier, and [surgically remove them]. However, even after [tumors are] cut out, we know that the patient has a good chance [of experiencing recurrence]. To be able to have another agent that can prevent that from happening and improve DFS is very important in all these [disease] stages, and regardless of PD-L1 status.

Is there anything else that you would like to add?

The more approvals we have, the more choices we will have to help patients with cancer. We will keep the trials going. I believe clinical trials are important. I encourage patients to go into clinical trials. There are still other variables that will need to be determined in the future, but this is a very positive day for the treatment of lung cancer.


FDA approves pembrolizumab as adjuvant treatment for non-small cell lung cancer. News release. FDA. January 26, 2023. Accessed February 1, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/

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