medwireNews: First-line treatment with atezolizumab significantly improves the overall survival (OS) of platinum-ineligible patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) relative to chemotherapy, suggest IPSOS trial data.
The PD-L1 inhibitor was associated with “a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy,” report Siow Ming Lee (University College London Hospitals NHS Foundation Trust, UK) and co-investigators.
“These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy,” a population that has been under-represented in pivotal clinical trials, they continue in The Lancet.
The phase 3 study enrolled 453 individuals with stage IIIB or IV disease lacking EGFR or ALK alterations who were considered unsuitable for platinum-doublet chemotherapy by the investigator because they had an ECOG performance status of 2 or 3 or were aged at least 70 years with substantial comorbidities or contraindications.
After a median follow-up of 41.0 months, the risk for death was reduced by a significant 22% among the 302 participants who were randomly assigned to receive atezolizumab 1200 mg on day 1 of each 21-day cycle compared with their 151 counterparts who instead received vinorelbine or gemcitabine in 3-weekly or 4-weekly cycles.
The median OS durations were 10.3 and 9.2 months, respectively, a difference that the researchers describe as “modest.”
However, they note that “many immunotherapy clinical trials show [that] the survival benefits only tend to become evident toward the later stages of treatment,” and indeed, the 2-year OS rate was doubled with atezolizumab, at 24% versus 12% with chemotherapy.
Furthermore, the objective response rate and median duration of response “were also approximately double with atezolizumab compared with chemotherapy,” adds the team, at 17% versus 8% and 14.0 versus 7.8 months, respectively.
Health-related quality of life also favored atezolizumab, with either clinically meaningful improvements or maintenance observed across all functioning domains and symptom scales, while chemotherapy was associated with clinically meaningful deteriorations in several functioning domains and symptoms.
Of note, atezolizumab treatment significantly reduced the time to confirmed deterioration in chest pain, “a key lung cancer symptom,” with a hazard ratio of 0.51 relative to chemotherapy, report Lee and colleagues.
With regard to safety, the team highlights that “no new or unexpected adverse events were identified with atezolizumab in this poor-prognosis population.”
Treatment-related adverse events of grade 3 or 4 occurred in a smaller proportion of patients in the atezolizumab than chemotherapy group, at rates of 16% versus 33%, as did treatment-related deaths, at 1% versus 3%.
The authors of an accompanying commentary say that although the trial was positive, “atezolizumab efficacy remains far from that observed in fit patients with ECOG [performance status] 0–1 with high PD-L1 expression tumours (2-year overall survival rate of around 45%), clearly confirming comorbidities and performance status as major prognostic variables.”
And even though immune checkpoint inhibitors are beneficial, they “do not result in marked absolute overall survival improvements in this population, leaving room for much efficacy improvement,” continue Hazel O’Sullivan (Cork University Hospital, Ireland) and Sanjay Popat (Institute of Cancer Research, London, UK).
Nevertheless, the commentators write: “IPSOS has identified a potential new indication for atezolizumab proving that randomized phase 3 trials can succeed in this population.
“We look forward to new trials of novel agents in this real-world population with more robust comorbidity and frailty measures embedded, to better understand the enrolled population, their risks, and aid patient selection for newer treatments.”
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Lancet 2023; doi:10.1016/S0140-6736(23)00774-2
Lancet 2023; doi:10.1016/S0140-6736(23)00807-3