The FDA recently approved atezolizumab, in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer (ES-SCLC).
This approval is based on results from the phase III IMpower133 study, which showed that atezolizumab in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (median overall survival [OS]=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the intention-to-treat (ITT) population.
The atezolizumab-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017). Safety for the atezolizumab and chemotherapy combination appeared consistent with the known safety profile of atezolizumab.
Atezolizumab is a monoclonal antibody designed to bind with the protein PD-L1. It is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the re-activation of T cells. Atezolizumab may also affect normal cells.
"Extensive-stage small cell lung cancer is a highly aggressive form of lung cancer, which until now, has seen limited treatment advances over the last 20 years," said Andrea Ferris, President and CEO of LUNGevity Foundation. "[This] approval of atezolizumab is an important step forward in ensuring that people across the spectrum of lung cancer types have effective new therapies."
IMpower133 is a phase III, multicenter, double-blinded, randomized placebo-controlled study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and etoposide versus carboplatin and etoposide alone in chemotherapy-naïve adults with ES-SCLC. The study enrolled 403 people who were randomized equally (1:1) to receive:
- Atezolizumab in combination with carboplatin and etoposide (Arm A), or
- Placebo in combination with carboplatin and etoposide (Arm B, control arm).
During the treatment-induction phase, people received treatment on 21-day cycles for 4 cycles, followed by maintenance with atezolizumab or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.
The co-primary endpoints were PFS as determined by the investigator using RECIST v1.1 and OS in the ITT population.
A summary of the ITT data from the IMpower133 study that support this approval is included below:
- Atezolizumab in combination with chemotherapy helped people live significantly longer compared to chemotherapy alone (OS=12.3 vs. 10.3 months; HR=0.70, 95% CI: 0.54-0.91; p=0.0069) in the ITT population.
- The atezolizumab-based combination also significantly reduced the risk of disease worsening or death compared to chemotherapy alone (PFS=5.2 vs. 4.3 months; HR=0.77; 95% CI: 0.62-0.96; p=0.017).
- Safety for the atezolizumab and chemotherapy combination appeared consistent with the known safety profile of atezolizumab. Serious adverse reactions occurred in 37 percent of people receiving atezolizumab plus chemotherapy compared with 35 percent of people receiving chemotherapy alone. The most common adverse reactions (≥20%) in people receiving atezolizumab plus chemotherapy were fatigue/asthenia (39%), nausea (38%), alopecia (37%), decreased appetite (27%), constipation (26%), and vomiting (20%).
Results from the study were simultaneously presented at the 2018 World Conference on Lung Cancer (WCLC) and published in The New England Journal of Medicine.
Atezolizumab is also approved in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adults with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. Additionally, atezolizumab is approved by the FDA to treat adults with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving atezolizumab.