Patients with lung cancer who were not fit enough to be recommended standard platinum doublet chemotherapy lived longer when treated with the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab than patients in a comparison group who received a single-agent chemotherapy regimen (Abstract LBA11). These are the findings of the open-label, international, Phase III randomized IPSOS study reported at the ESMO Congress 2022.
In the absence of data-driven evidence from randomized investigations, patients with lung cancer who had low performance status had no proven options for initial treatment.
"In reality, we have this large unfit non-small cell lung cancer population who we just simply cannot treat with standard doublet chemotherapy. And we treat them either with single-agent chemotherapy or we offer them best supportive care," noted Siow Ming Lee, PhD, FRCP, Chair of the IPSOS trial, Professor of Medical Oncology at University College London, and Consultant Medical Oncologist at University College London Hospital. "You have to remember that first-line immunotherapy trials-with or without chemotherapy-were restricted to fit patients-performance status 0 and 1. And also, their median age was 65 or less."
Lee inspired his audience at the ESMO Congress by explaining how the IPSOS investigators had set out specifically to target unfit patients with lung cancer-those who make up the majority of lung cancer cases in typical thoracic oncology centers. This was in complete contrast to pivotal drug efficacy trials that had generally selected patients with good performance status. With clinicians being left to guess about the best options for their many unfit patients, the IPSOS investigators set out to satisfy this unmet need.
The IPSOS study revealed dramatic improvement in outcomes among these patients: a doubling of response rates among patients in the investigational study arm treated with atezolizumab compared with patients in the control group treated with chemotherapy, and a big improvement in overall survival.
Study Details
The IPSOS study was simple, Lee noted, randomizing unfit patients with Stage 3B or 4 disease to atezolizumab or single-agent chemotherapy with gemcitabine or vinorelbine until disease progression. The primary endpoint had been overall survival.
"We met the objective [with a] hazard ratio of 0.78. We got a very impressive 1-year survival [rate]-44 percent. And more impressively, 24 percent [were] alive at 2 years. So, we are talking about one in four patients alive on the immunotherapy treatment, which is a pretty impressive result," Lee told Oncology Times.
The backdrop to this research had been that atezolizumab had already been shown to improve overall survival (OS) in comparison with platinum doublet therapy in patients whose NSCLC had high PD-L1 expression and who had good ECOG performance status (1 or 0). But the IPSOS investigators were aware that more than 40 percent of patients with NSCLC had poor ECOG performance status (2 or more) with many of them also having substantial comorbidities, making them ineligible for standard chemotherapy combinations.
A total of 453 patients were randomized-302 to atezolizumab and 151 to chemotherapy. The patients had a median age of 75. Nearly a third of them were at least 80. After a median follow-up of 41 months, immunotherapy had significantly improved OS in comparison with chemotherapy, with a consistent benefit seen across key subgroups-including those defined by PD-L1 expression levels, performance status, and histology.
As well as the benefit in the 2-year OS rate and the response rate, the toxicity data showed an advantage for patients in the immunotherapy arm, with Grade III or IV events occurring in 16.3 percent of patients on atezolizumab compared with 33.3 percent in the chemotherapy arm of the study. Deaths were nearly 3 times more common in the chemotherapy group. There was a near doubling of time to chest pain with atezolizumab compared with chemotherapy and "meaningful" improvements from baseline were also seen for appetite loss and cough.
The investigators concluded that the option of atezolizumab had improved OS in comparison with chemotherapy among platinum-ineligible patients with NSCLC-with twice as many patients estimated to be alive at 2 years when treated with atezolizumab rather than chemotherapy and no new or unexpected safety concerns in this poor prognosis population.
"These are probably the most impressive results that we have seen for these poor prognosis patients-elderly [with] co-morbid problems," Lee said, noting this followed 20 years of no significant progress for this group. "And this is the first time we've shown this treatment alone improves survival significantly for this poor, elderly population with non-small cell lung cancer."
Peter M. Goodwin is a contributing writer.