EMPOWER-Lung 3 (Abstract #LBA51) - Cemiplimab in combination with platinum doublet chemotherapy for first-line (1L) treatment of advanced Non-small cell lung cancer (NSCLC)
Regeneron and Sanofi's jointly developed Libtayo (cemiplimab) is approved as monotherapy for first-line treatment of NSCLC with tumors having high PD-L1 expression. The drug also has cutaneous squamous cell carcinoma and basal cell carcinoma on its label. The drug shined on the 4th day of ESMO 2021, with the presentation of positive results from the Phase III EMPOWER-Lung 3 trial, which investigated the first-line combination treatment of Libtayo and platinum-doublet chemotherapy in patients with squamous and non-squamous advanced NSCLC, irrespective of PD-L1 expression. The trial met its primary as well as key secondary endpoints and is one of two PD-(L)1 inhibitors to demonstrate positive Phase III results in first-line advanced NSCLC, irrespective of histology both as monotherapy and in combination with chemotherapy, following Keytruda (pembrolizumab). Moreover, the EMPOWER-Lung 3 trial was finished early as Libtayo significantly improved overall survival compared to chemotherapy; this landmark was achieved considering that we already have Libtayo approved as a monotherapy.
In the overall population, patients treated with the Libtayo combination (n = 312) experienced 22-month median OS compared to 13 months for those receiving chemotherapy alone (n = 154), thereby demonstrating a 29% relative reduction in the risk of death. Meanwhile, the 12-month probability of survival for the Libtayo combination was 66% and 56% for chemotherapy. When comparing the median progression-free survival (PFS), an 8-month median PFS was observed in patients treated with the Libtayo combination, as opposed to 5 months for chemotherapy, showcasing a 46% relative reduction in the risk of disease progression. Additionally, the 12-month probability of PFS was 38% for the Libtayo combination and 16% for chemotherapy. The objective response rate (ORR) was 43% versus 23%, while the median duration of response (DOR) was 16-months compared to 7 months for the Libtayo combination versus chemotherapy, respectively.
Libtayo combination demonstrated delayed deterioration in pain symptoms. Grade 3 or higher AEs were more common in the cemiplimab arm (43.6%) than in the chemotherapy and placebo arm (31.4%).
Expert opinion- "Libtayo added to chemotherapy significantly improved patient outcomes, extending median overall survival to 22 months and median progression-free survival to 8 months. Exploratory analyses showed that survival improvements were seen across squamous and non-squamous histologies and in patients with reduced daily functioning, with 43% of patients having squamous disease and 84% having an ECOG 1 performance status. Furthermore, in another exploratory analysis, the Libtayo combination helped delay deterioration in patient-reported quality of life and pain symptoms."
- Expert Opinion
INSIGHTS- Regeneron and Sanofi are planning to use these promising results for regulatory submission in the US and EU. The NSCLC space is not an easy nut to crack as there are various established therapies already flourishing in the market. However, with Libtayo's existing approval as monotherapy for NSCLC, another approval in combination with chemotherapy should not be that difficult. The challenging part would be carving a place for itself in the highly competitive NSCLC market. But the advantage associated with Libtayo is its fair price and the company expects to play the price card in the market in comparison to other high-priced established anti-PD-1s.
Competition against key players like Keytruda (KEYNOTE-189 and KEYNOTE-407), Yervoy, Opdivo duo in combination with chemotherapy (CHECKMATE 9LA), and others would be worth watching. Keytruda could be a tough competitor for Libtayo as both prolonged the patient survival by 22 months in non-squamous NSCLC patients, while the reduction in the risk of death was 51% in KEYNOTE-189 as compared to 29% in EMPOWER-Lung 3. A more straightforward comparison could be made with the Opdivo-Yervoy duo with chemotherapy combo, which secured their front-line NSCLC approval in May 2020. This duo-immunotherapy cut the patients' risk of death by 31% over chemo while providing a median survival of 14.1 months versus 10.7 months for chemo. As per Delveinsight's analysis, the drug manufacturers need to be quite vigilant with Libtayo's niche market and need to plan their commercialization strategies, including possible reimbursement and market access plans for the patients.
Other emerging key players alongside the Libtayo-chemo combination are Eli Lilly and Innovent Biologics' Tyvyt (Sintilimab)-Alimta and platinum chemotherapy combination as well as AstraZeneca's Imfinzi (anti-PD-L1)-Tremelimumab (anti-CTLA-4) and chemotherapy combination. The Chinese biopharmaceutical has already submitted the biologics license application (BLA) for their combination and has been accepted for FDA review in May 2021. On the other hand, Delveinsight remains quite uncertain about the success of AstraZeneca's trio as anti-CTLA-4 combinations do not perform really well and also sometimes come up with the cost of additional toxicities associated with them. Moreover, the Imfinzi-Tremelimumab combo failed the phase III MYSTIC and NEPTUNE lung cancer trials. It would be now interesting to watch its direct competition with the BMS trio and other established key players in the market.