Immunotherapy for lung cancer has added another reggie! Libtayo combination therapy is expected to become a first-line new solution
Recently, the FDA has accepted the review of Libtayo (cemiplimab) combined with chemotherapy for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) complementary biological product license application (sBLA). The latest trial results show that in this patient group, Libtayo combination therapy can significantly improve total survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) compared with chemotherapy alone.
Libtayo combination therapy trial data
This application is supported by the results of the ENABLE-Lung PHASE 3 trial (NCT03409614). The main endpoint of the trial is OS, and the key secondary endpoints include PFS and ORR. Other secondary endpoints include DOR, optimal total response, safety, and patient-reported results. The trial recruited patients with advanced NSCLC with ineffective treatment, non-squamous and squamous histology, stage IIIB/C and IV diseases, with ECOG manifestations of 0 or 1. Patients can have any PD-L1 expression, allowing patients with treated and clinically stable central nervous system metastases. Patients cannot have tumors carrying EGFR, ALK, or ROS1 mutations.
A total of 466 participants randomly received Libtayo in a 2:1 ratio, once every 3 weeks, and at the same time received the platinum dual-drug chemotherapy selected by the researcher, once every 3 weeks, for a total of 4 cycles (n=312), or placebo, once every 3 weeks, and at the same time received the platinum dual-drug chemotherapy selected by the researcher, once every 3 weeks, for a total of 4 cycles (n=312), or placebo, once every 3 weeks, and at the same time received the platinum dual-drug chemotherapy selected by the researcherDual-drug chemotherapy, the same time (n = 154). Treatment lasts until the disease progresses or up to 108 weeks.
Patients were stratified according to PD-L1 expression (less than 1% vs 1% to 49% vs 50% or higher) and histology (non-scaly vs scaly). Most patients (84.3%) had an ECOG performance status of 1, and 6.7% of patients had brain metastases. In addition, 85.2% of patients had metastatic diseases at the time of screening, and 14.8% had locally advanced diseases. Approximately half of the patients (53.2%) are currently smokers. The median age of the 466 participants was 63.0 years old (range 25-84 years old), and 40.3% were 65 years old or above. In addition, 83.9% are men. Regarding histology, 57.1% of people have non-squamous diseases and 42.9% have squamous diseases. In addition, 29.8% of patients had PD-L1 expression less than 1%, 37.6% had expression between 1% and 49%, and 32.6% had expression at 50% or more.
All 312 patients in the Libtayo group received treatment, and as of the data cutoff date of June 14, 2021, 108 were still receiving treatment. In the control group, 153 out of 154 patients received treatment, and only 15 were still receiving treatment at the data cutoff. In the Libtayo/chemotherapy group, 204 patients discontinued treatment due to disease progression (n = 137), death (n = 24), toxicity (n = 14), patient decision (n = 13), withdrawal of consent (n = 8), physician decision (n = 4), and loss of follow-up (n = 1).
Trial data presented at the 2021 ESMO Congress showed that the median overall survival (OS) with the addition of Libtayo was 21.9 months (95% CI, 15.5–non-evaluable [NE]), while the OS with chemotherapy alone was 13.0 months (95% CI, 11.9–16.1) (HR, 0.71; 95% CI, 0.53–0.93; P=0.014). The 12-month OS rates in the study group and the control group were 65.7% (95% CI, 59.9%–70.9%) and 56.1% (95% CI, 47.5%–63.8%), respectively.
The median progression-free survival (PFS) for combination therapy was 8.2 months (95% CI, 6.4–9.3), while that for chemotherapy alone was 5.0 months (95% CI, 4.3–6.2) (HR, 0.56; 95% CI, 0.44–0.70; P<0.0001). The 12-month PFS rates for Libtayo and the control group were 38.1% (95% CI, 32.4%–43.8%) and 16.4% (95% CI, 10.5%–23.4%), respectively.
This combination also resulted in an ORR of 43.3% (95% CI, 37.7%–49.0%), compared to an ORR of 22.7% (95% CI, 16.4%–30.2%) for chemotherapy alone (odds ratio, 2.68; 95% CI, 1.72–4.19; P<0.0001). Among patients who responded to Libtayo plus chemotherapy, 40.7% achieved a partial response and 2.6% achieved a complete response; in the chemotherapy alone group, these rates were 22.7% and 0%, respectively. Furthermore, the median DOR was 15.6 months (95% CI, 12.4–NE) in the study group and 7.3 months (95% CI, 4.3–12.6) in the control group.
Compared with chemotherapy alone, the use of Libtayo plus chemotherapy resulted in a delayed time to final clinically significant deterioration in Global Health Score (GHS)/Quality of Life (QoL) (HR, 0.78; 95% CI, 0.51–1.19; P = 0.248) and pain symptoms (HR, 0.39; 95% CI, 0.26–0.60; P < 0.0001). Furthermore, compared with the control group, the overall changes in GHS/QoL (0.61; 95% CI, -2.23 to 3.45; P = .673) and pain symptoms (-4.98; 95% CI, -8.36 to -1.60; P = .004) were also improved in the survey group.
In addition, the combination of Libtayo and chemotherapy has an acceptable benefit-risk profile. In the Libtayo treatment group, 96% of patients had any level of sudden adverse reactions to treatment (TEAEs), while in the control group, 94% of patients had TEAEs; 4% and 3% of patients reported grade 3-5 TEAEs, respectively. 5% of patients in the study group had any level of TEAEs, and 3% of patients in the control group had any level of TEAEs, resulting in treatment interruption; 4% and 3% of patients had level 3 to 5 TEAEs, resulting in treatment interruption.
Introduction of new Libtayo immunotherapy drugs
Product name: Libtayo
Drug name: Cemiplimab
Manufacturer: Sanofi, Regeneron
Libtayo is a whole-person monoclonal antibody that targets the immune checkpoint receptor PD-1 on T cells. By binding to PD-1, the drug has been shown to prevent cancer cells from inhibiting the activation of T cells through the PD-1 pathway. In the United States, the European Union and other countries, Libtayo has been approved for the treatment of adult patients with metastatic or locally advanced skin squamous cell carcinoma (CSCC) who are not suitable for radical surgery or radical radiotherapy. In addition, Libtayo is the first immunotherapy approved for the treatment of basal cell carcinoma (BCC).
Reminder: Based on its promising anti-cancer activity and tolerable safety, Libtayo combined chemotherapy is expected to become a new first-line treatment option for advanced non-small cell lung cancer. We look forward to the early approval of this therapy and its clinical application for the benefit of more patients.
