Atezolizumab Improves Overall Survival in Platinum-Ineligible NSCLC

The rate of 2-year overall survival was nearly doubled with atezolizumab vs vinorelbine or gemcitabine in advanced platinum-ineligible non–small cell lung cancer.

Treatment with atezolizumab (Tecentriq) led to an almost doubled rate of 2-year overall survival (OS) vs vinorelbine or gemcitabine in patients with advanced platinum-ineligible non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 IPSOS trial (NCT03191786).

Findings from the study, which were presented at the 2022 ESMO Congress with a median follow-up of 41.0 months, demonstrated that the median OS was 10.3 months (95% CI, 9.4-11.9) with atezolizumab (n = 302) vs 9.2 months (95% CI, 5.9-11.2) with chemotherapy (n = 151), resulting in a 22% reduction in the risk of death with the PD-L1 inhibitor (HR, 0.78; 95% CI, 0.63-0.97; P = .028). The 12-month OS rate was 43.7% with atezolizumab vs 38.6% with chemotherapy. Moreover, the 24-month OS rate with atezolizumab was approximately double that with chemotherapy, at 24.3% and 12.4%, respectively.

“Many patients with advanced stage lung cancer cannot tolerate standard platinum-based chemotherapy. IPSOS is a randomized phase 3 trial to examine the role of immunotherapy with first-line atezolizumab for advanced stage NSCLC patients deemed not eligible to receive platinum-based chemotherapy treatments because of poor performance status [PS] or elderly with significant contraindications,” said lead study author Siow Ming Lee, MD, PhD, FRCP, professor of medical oncology at University College London Hospitals.

Approximately 40% of patients with advanced NSCLC have an ECOG PS of at least 2 and/or significant comorbidities rendering them ineligible for platinum-doublet chemotherapy. As such, IPSOS was designed to evaluate the efficacy of immune monotherapy in a population that has been historically excluded from clinical trials with first-line immunotherapy.

Eligible patients had treatment-naïve, stage IIIB/IV, squamous or nonsquamous NSCLC per the AJCC 7th edition. Reasons for platinum ineligibility included an ECOG PS of 2 or 3 or age of at least 70 years and substantial comorbidities or contraindications to platinum in the context of a PS of 0 or 1. Patients with treated, asymptomatic brain metastases were permitted. Those with EGFR or ALK alterations were excluded. Patients were stratified by PD-L1 status but it was not an inclusion criteria.

Patients were randomly assigned 2:1 to 1200 mg of intravenous (IV) atezolizumab every 3 weeks until progressive disease (PD) or loss of clinical benefit; or either oral or IV vinorelbine or IV gemcitabine, both dosed by the local primary investigator until PD. Median age was 75 years and 31% were 80 or older. Eighty-three percent had ECOG PS of 2 or more.

The primary end point was OS, with secondary end points of 6-, 12-, 18-, and 24-month OS rates, progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and OS and PFS in the PD-L1–positive subgroups.

Additional findings demonstrated that the ORR was 16.9% (95% CI, 12.8%-21.6%)with atezolizumab vs 7.9% (95% CI, 4.2%-13.5%) with chemotherapy, reflecting an absolute difference of 8.9% (95% CI, 2.4-15.5). The median DOR was 14.0 months (95% CI, 8.1-20.3) with atezolizumab vs 7.8 months (95% CI, 4.8-9.7) with chemotherapy.

QOL as assessed by the EORTC QLQ-C30 and QLQ-LC13 functioning scales and symptoms questionnaires indicated that role function, cognitive function, and social function remained stable or were improved from baseline to week 48 of treatment with atezolizumab. Notably, the median time to confirmed deterioration of chest pain was not estimable in either arm but favored the use of atezolizumab (HR, 0.51; 95% CI, 0.27-0.97).

Additionally, meaningful changes were reported across several disease- and treatment-related symptoms, including an improvement in appetite loss and cough with atezolizumab, an improvement in insomnia with chemotherapy, and a worsening of appetite loss, peripheral neuropathy, and alopecia with chemotherapy.

Lee noted that no new or unexpected safety concerns occurred with atezolizumab. The median treatment duration (3.5 months vs 2.3 months and 1.8 months) and number of cycles started (6 vs 4 and 3) was higher in the atezolizumab arm vs the gemcitabine and vinorelbine arms, respectively.

Treatment-related adverse effects (TRAEs) occurred in 57.0% (n = 171) of patients in the atezolizumab arm vs 80.3% (n = 118) of those in the chemotherapy arm. Grade 3/4 TRAEs occurred in 16.3% (n = 49) and 33.3% (n = 49) of patients in the atezolizumab and chemotherapy arms, respectively. Serious TRAEs were experienced by 11.7% (n = 35) and 15.6% (n = 23) of patients, respectively. Three treatment-related fatalities occurred in the atezolizumab arm vs 4 in the chemotherapy arm.

AEs leading to drug discontinuation were comparable between arms, at 13.0% (n = 39) and 13.6% (n = 20) with atezolizumab and chemotherapy, respectively. AEs leading to drug modification or interruption occurred less frequently with atezolizumab at 32.0% (n = 96) vs 48.3% (n = 71) with chemotherapy.

“For over two decades, clinical trials have not brought significant improvement for this population. IPSOS is the first randomized trial to show that first-line atezolizumab treatment significantly improves OS compared with single-agent chemotherapy for these poor prognosis patients with no EGFR and ALK alterations,” said Lee. “Twice as many patients remained alive at 2 years when treated with atezolizumab. OS benefit was seen regardless of patients’ age, histology, PD-L1 status and ECOG PS. Atezolizumab also stabilized and/or improved some HRQOL measures with no new safety signals identified.”

Reference
Lee SM, Schulz C, Prabhash K, et al. IPSOS: results from a phase 3 study of first-line (1L) atezolizumab vs single-agent chemotherapy in patients with NSCLC not eligible for a platinum-containing regimen. Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089