Ana Baramidze, MD, provides background on the FDA approvals of cemiplimab in NSCLC, expands on key efficacy and safety data with cemiplimab from EMPOWER-Lung 3, and discusses the current treatment landscape for patients with advanced NSCLC.
As the second FDA-approved PD-1 inhibitor to improve outcomes in newly diagnosed patients with non–small cell lung cancer (NSCLC) as both a single agent and in combination with chemotherapy, cemiplimab-rwlc (Libtayo) plus platinum-based chemotherapy, now approved in NSCLC, broadens the potential benefits of PD-1 inhibition and expands treatment options for an array of patient subgroups, according to Ana Baramidze, MD.
On November 8, 2022, the FDA approved cemiplimab in combination with platinum-based chemotherapy as first-line therapy in adult patients with advanced NSCLC harboring no EGFR, ALK, or ROS1 mutations, based on findings from the phase 3 Study 16113/EMPOWER-Lung 3 trial (NCT03409614).1
Results from this study demonstrated that cemiplimab plus chemotherapy elicited a significantly improved overall survival (OS) compared with chemotherapy alone, with a median OS of 21.9 months (95% CI, 15.5-not evaluable) and 13.0 months (95% CI, 11.9-16.1), respectively. Furthermore, the median progression-free survival (PFS) increased from 5 months (95% CI, 4.3-6.2) with chemotherapy alone to 8.2 months (95% CI, 6.4-9.3) with the combination.
Based on OS and PFS data, cemiplimab resulted in a 29% reduction in the risk of death (HR, 0.71; 95% CI, 0.53-0.93; 2-sided P = .0140), and a 44% reduction in the risk of disease progression or death (HR, 0.56; 95% CI, 0.44-0.70; P < .0001).
“The approval of this combination expands the use of cemiplimab to patients with all levels of PD-1 expression and tumor histology and provides an important option for physicians to consider [for] appropriate patient [subgroups],” said Baramidze, who is the head of the Clinical Research Department at the Research Institute of Clinical Medicine, Todua Medical Center, Tbilisi, Georgia.
In an interview with OncLive®, Baramidze provided background on the previous approval of cemiplimab in NSCLC, expanded on key efficacy and safety data with cemiplimab from EMPOWER-Lung 3, and discussed the influence of this approval on the current treatment landscape for patients with advanced NSCLC.
Baramidze:This approval is significant because it provides a new first-line treatment option for patients who have either metastatic or locally advanced disease, no EGFR, ALK, or ROS1 aberrations, and are not candidates for surgical resection or definitive chemoradiation. Importantly, this marks the second approval for cemiplimab in advanced NSCLC. It expands the patient population [that is] eligible to be treated with cemiplimab to now include all levels of PD-L1 expression and tumor histologies when used in combination with chemotherapy.
Unfortunately, lung cancer remains 1 of the most common cancers worldwide, with more than 2.2 million new cases diagnosed each year. Because there are a variety of clinical characteristics that each patient can present with, having multiple options is crucial.
Cemiplimab is a fully human monoclonal antibody targeting PD-1, a human checkpoint receptor on T cells. [It] blocks cancer cells from using the PD-1 pathway to suppress T-cell activation. The addition of chemotherapy [to cemiplimab] can be considered in appropriate patients with any level of PD-L1 expression [in their] tumor histology to drive a clinical response.
The cemiplimab and chemotherapy combination was approved [in NCSLC] based on results from the EMPOWER-Lung 3 trial, which allowed for the enrollment of patients with [several] disease presentations [that] physicians manage every day in clinical practice. [The study population] covered a wide variety of patients, [including those with] inoperable, locally advanced disease not suitable for definitive chemoradiation; treatment-naïve stage IV disease; and pretreated, clinically stable brain metastases. Patients with uncontrolled viral infection and [those who were] nonsmokers [were excluded from enrollment].
Notably, the use of cemiplimab extended survival in advanced NSCLC both as a monotherapy in PD-L1–high disease and in combination with chemotherapy irrespective of PD-L1 expression level. This has only been achieved by 1 other PD-1 inhibitor before.
In EMPOWER-Lung 3, patients treated with the combination of cemiplimab and chemotherapy [experienced] improved OS compared [with] those treated with chemotherapy alone. The median OS [was] 21.9 months vs 13.0 months, [respectively, resulting in a] 29% relative reduction in the risk of death. [Furthermore,] the estimated 12-month [OS rate] was 65.7% with the cemiplimab combination vs 56.1% with chemotherapy alone. There was also significant improvement in PFS, overall response rate [ORR] and duration of response [DOR].
The median PFS was [8.2] months with cemiplimab plus chemotherapy vs 5.0 months with just chemotherapy, [resulting in] a 44% reduction in the risk of disease progression or death. The estimated 12-month PFS rate with the combination was 38.1% vs 16.4% with chemotherapy. The ORR [was] 43.3% with cemiplimab plus chemotherapy vs 22.7% with chemotherapy alone. Additionally, treatment with cemiplimab plus chemotherapy resulted in a [15.6]-month median DOR vs [7.3] months in the chemotherapy arm.
Cemiplimab combined with chemotherapy demonstrated a favorable safety profile with no [surprising] safety signals observed. Common [adverse events (AEs)] occurring [in] at least 15% of patients were alopecia, musculoskeletal pain, nausea, fatigue, peripheral neuropathy, and decreased appetite. This profile was consistent with data previously observed with these agents. Treatment discontinuation because of AEs occurred in [5.1% of patients], and [fatal reactions occurred in] 6.1% of patients.
[This approval] expands the patient population [that is] eligible to be treated with cemiplimab to now include all levels of PD-L1 expression and tumor histology and provides an important option for physicians to consider [for] appropriate patients. It’s just 1 of 2 PD-1 inhibitors approved in the US [in NSCLC] that can be used both as a monotherapy in patients with high PD-L1 expression, and in combination with chemotherapy irrespective of PD-L1 expression level.
Despite having these approved options, advanced NSCLC remains a leading cause of cancer deaths worldwide. It’s important to continue researching and developing PD-1 inhibitors and potential combinations.
[Notably], cemiplimab is not yet approved in the European Union for this indication. The European Medicines Agency is currently reviewing the application, and a decision is expected in the coming months.
FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. News release. FDA. November 8, 2022. Accessed January 24, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/