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The European Commission has approved atezolizumab for use as a frontline treatment in patients with metastatic non–small cell lung cancer whose tumors have a high PD-L1 expression and do not harbor EGFR or ALK aberrations.
The European Commission has approved atezolizumab (Tecentriq) for use as a frontline treatment in patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a high PD-L1 expression and do not harbor EGFR or ALK aberrations.1
The regulatory decision was based on data from the phase 3 IMpower110 trial (NCT02409342), which showed that single-agent atezolizumab improved overall survival (OS) by 7.1 months vs chemotherapy. The median OS in the investigative arm was 20.2 months vs 13.1 months in the control arm (HR, 0.59; 95% CI, 0.40-0.89; P = .0106).2
“We are delighted to bring [atezolizumab] to people in the European Union with this specific type of lung cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “[Atezolizumab] monotherapy has been shown to improve OS in people with high PD-L1 expression, when compared with chemotherapy, and therefore represents a new treatment option for people living with this difficult-to-treat disease.”
In the open-label, phase 3 trial, investigators examined the safety and efficacy of atezolizumab monotherapy vs cisplatin or carboplatin and pemetrexed or gemcitabine in PD-L1–selected, chemotherapy-naïve patients with stage IV nonsquamous or squamous NSCLC. A total of 572 patients were enrolled to the trial, and 554 of these patients were included in the intent-to-treat population, which excluded those with EGFR or ALK aberrations.
To be eligible for participation, patients needed to be at least 18 years of age, have measurable disease per RECIST v1.1 criteria, have an ECOG performance status of 0 or 1, and could not have received prior chemotherapy. PD-L1 expression on at least 1% of tumor cells or tumor-infiltrating immune cells covering at least 1% of the tumor was required.
Study participants were randomized 1:1 to receive either intravenous atezolizumab at a dose of 1200 mg or 4 to 6 cycles of platinum-based chemotherapy once every 3 weeks. In the control arm, those with nonsquamous disease were given either cisplatin or carboplatin plus pemetrexed, while those with squamous disease were given cisplatin plus gemcitabine or carboplatin plus gemcitabine.
The primary end point of the trial was OS in the PD-L1–selected population that excluded those with EGFR or ALK aberrations. Secondary end points comprised investigator-assessed progression-free survival (PFS) per RECIST v1.1 criteria, the occurrence and duration of a response, and overall and investigator-assessed PFS per RECIST v1.1 criteria in prespecified subgroups with respect to PD-L1 expression and blood-based tumor mutational burden.
Additional data revealed that at the time of data cutoff, 71.2% of patients with EGFR and ALK wild-type tumors who had high PD-L1 expression either experienced progression or died. The median PFS was 8.1 months in the investigative arm vs 5.0 months in the control arm (stratified HR, 0.63; 95% CI, 0.45-0.88). In patients with EGFR and ALK wild-type tumors with high or intermediate PD-L1 expression, the median PFS was 7.2 months and 5.5 months in the atezolizumab and chemotherapy arms, respectively (stratified HR, 0.67; 95% CI, 0.52-0.88).
Moreover, 38.3% of patients with EGFR and ALK wild-type tumors and high PD-L1 expression experienced an investigator-assessed confirmed response (CR) to treatment in the investigative arm vs 28.6% of those in the control arm. Confirmed responses were ongoing in 68.3% and 35.7% of those on the atezolizumab and chemotherapy arms, respectively, at the time of data cutoff.
In patients with EGFR and ALK wild-type tumors with high or intermediate PD-L1 expression, 30.7% and 32.1% of patients on the investigative and control arms, respectively, experienced an investigator-assessed CR. Confirmed responses were ongoing in 70.6% and 34.6% of patients, respectively.
Among patients who had a high PD-L1 expression per the SP142 assay, the median OS with atezolizumab was 20.2 months vs 13.1 months with chemotherapy (stratified HR, 0.59; 95% CI, 0.40-0.89). Those with a tumor proportion score of at least 50% per the 22C3 assay had an OS of 20.2 months with atezolizumab vs 11.0 months with chemotherapy (unstratified HR, 0.60; 95% CI, 0.42-0.86). For those with PD-L1 expression on at least 50% of tumor cells per the SP263 assay, the OS was 19.5 months and 16.1 months in the investigative and control arms, respectively (unstratified HR, 0.71; 95% CI, 0.50-1.00).
Updated data from an exploratory OS analysis done in the PD-L1–high population showed a continued OS benefit with atezolizumab at a median follow-up of 31.3 months (HR, 0.76; 95% CI, 0.54-1.09).3 The median OS in the atezolizumab arm was the same as what had been reported at the prior analysis, 20.2 months, vs 14.7 months in the chemotherapy arm.
Regarding safety, 90.2% of patients in the investigative arm vs 94.7% of those in the control arm experienced adverse effects (AEs); grade 3 or 4 AEs were reported in 30.1% and 52.5% of patients, respectively. The most frequently experienced AEs with atezolizumab included anemia, neutropenia, and thrombocytopenia. Serious AEs were experienced by 28.3% of those in the atezolizumab arm vs 28.5% of those in the chemotherapy arm. Grade 5 AEs were reported in 3.8% and 4.2% of patients, respectively.