Dr Tamta Makharadze Discusses EMPOWER-Lung 3 Data for Frontline Cemiplimab Plus Chemo in Advanced NSCLC

The benefits of adding cemiplimab (Libtayo, Regeneron) to platinum-doublet chemotherapy in the frontline setting for patients with advanced non advanced non–small cell lung cancer (NSCLC) was sustained after more than 2 years, regardless of histology or level of PD-L1 expression, according to follow-up data from the phase 3 EMPOWER-Lung 3 trial (NCT03409614).¹

Makharadze

Data presented last month at the European Lung Cancer Congress in Copenhagen, Denmark, showed that at a median follow-up of 28.4 months, patients taking the cemiplimab plus chemotherapy combination had a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.51-0.82; P = .0003), with a median OS of 21.1 months (95% CI, 15.9-23.5) vs 12.9 months (95% CI, 10.6-15.7) for chemotherapy alone. Investigators estimated OS rates at 24 months in the study and control arms were 42.7% and 27.2%.

EMPOWER Lung-3 had randomized patients 2:1 in the treatment and control arms (312 vs 154); all were treatment-naïve with nonsquamous or squamous histology and stage IIIB/C or stage IV NSCLC. Patients were required to have an ECOG performance status of 0 or 1, but could not have EGFR, ALK, or ROS1 aberrations; any PD-L1 expression level was permitted.^2,3

EMPOWER-Lung 3 had previously reported a 29% reduction in the risk of death in the primary analysis;³ based on these data, FDA in November 2022 approved cemiplimab plus platinum-based chemotherapy for adult patients with advanced NSCLC whose tumors did not harbor EGFR, ALK or ROS1 aberrations.⁴

The results presented in Copenhagen were the final OS data as of June 14, 2022, when the study reached a prespecified data cutoff of 291 deaths.¹ Tamta Makharadze, MD, lead study author and medical oncologist at LTD High Technology Hospital Medical Center, in Batumi, Georgia, presented the data at the Congress and discussed the findings in a follow-up interview with Evidence-Based Oncology (EBO). The following interview has been edited lightly for clarity.

EBO: As we look at these updated data from EMPOWER-Lung 3 compared with the previously reported results, both the median OS and the median duration of response (DOR) for the cemiplimab and chemotherapy combo are improved relative to chemotherapy alone. Can you discuss the importance of these findings?

Makharadze: The longer-term data from the pivotal EMPOWER-Lung 3 trial are significant. They confirmed the durability of survival improvements with cemiplimab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer, with no EGFR, ALK, ROS1, or irrespective of histology or PD-L1 expression level. Specifically, after a median follow-up of 28 months, we are continuing to see significant improvement in overall survival and progression-free survival in patients receiving the cemiplimab plus chemotherapy versus chemotherapy alone. This includes a median overall survival of 21.1 month for cemiplimab plus chemotherapy compared to 12 months for chemotherapy alone, representing a 35% reduction in the risk of death. Median progression-free survival was 8 months for cemiplimab plus chemotherapy versus 5 months for chemotherapy alone. Now, additionally, objective response rates are 44% for cemiplimab plus chemotherapy versus 22% for chemotherapy alone with a duration of response of 16 months versus 7 months.

EBO: Is there a particular data point among the ones that you just mentioned that you think is particularly important for US payers, in terms of highlighting one thing that is particularly compelling for reimbursement purposes?

Makharadze: With this particular data presentation of longer-term data, from across all patients enrolled through the trial, it is notable that the study was designed to a closely resemble a patient population with the varied disease presentations seen in everyday clinical practice. Specifically, among those enrolled, 43% had squamous histology, 15% had locally advanced disease, [and] 7% had a history of brain metastases.

EBO: The results at 28 months show that the safety profile is very consistent with what the trial has reported previously. What are clinicians learning about managing the side effects with the cemiplimab-chemo combination?

Makharadze: In assessing outcomes after a median of 28 months of follow up, we learned that cemiplimab plus chemotherapy continued to show an acceptable safety profile compared to chemotherapy alone. These findings were also supported by favorable patient-reported outcomes, where improvements in pain symptoms indicated that cemiplimab plus chemotherapy demonstrated a good benefit-risk profile, but it does not impose toxicity that interferes with the quality of life.

EBO: There were a small number of patients in which cemiplimab plus chemotherapy demonstrated a complete response. Are there any common characteristics among this group of patients?

Makharadze: There were 13 complete responses with all the responses occurring in patients who received the cemiplimab and chemotherapy combination. And there was a significant difference in objective response rate. So, we are seeing that cemiplimab with chemotherapy shows significantly better responses than chemotherapy alone.

References

1. Makharadze T, Gogishvili M, Melkadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in advanced non-small cell lung cancer: 2-year follow-up results from the phase 3 EMPOWER-Lung 3 part 2 trial. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 50.
2. Caffrey M. Frontline cemiplimab with chemo offers benefits in advanced NSCLC regardless of PD-L1 status. The American Journal of Managed Care website. September 19, 2021. Accessed April 21, 2023. https://www.ajmc.com/view/frontline-cemiplimab-with-chemo-offers-benefits-in-advanced-nsclc-regardless-of-pd-l1-status
3. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022;28(11):2374-2380. doi:10.1038/s41591-022-01977-y
4. FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. FDA. November 8, 2022. Accessed April 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/