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Immunotherapy as an Alternative to Chemotherapy in the Elderly Lung Cancer Patient: IPSOS Trial

Dr. Solange Peters, President of the European Society for Medical Oncology, presents during the first-ever US-based ESMO Conference – 2022 ESMO Florida.

In the first-ever ESMO Review session held in the United States, ESMO president Dr Solange Peters discussed the emerging role of immunotherapy in the treatment of non-small cell lung cancer (NSCLC). She first noted the overall survival (OS) difference when comparing squamous cell and non-squamous cell lung cancers since the year 2000, highlighting the continued dismal outcomes for squamous histology. She noted that survival has improved with the use of immunotherapies (~ 1.5 to 2.0 years), when used both alone, and with chemotherapy, and emphasized that immunotherapy is now a standard frontline treatment for patients with metastatic NSCLC. Dr Peters noted that programmed death ligand-1 (PD-L1) expression is predictive of immunotherapy benefit, with 50% or more PD-L1 expression now accepted as a threshold for efficacy of immunotherapy over chemotherapy; for example at 3 years’ follow up for patients with >50% PD-L1 expression, cemiplimab was associated with significantly longer OS as compared with chemotherapy (26.1 vs. 13.3 mo; P=0.0001) and a significantly longer progression-free survival (8.1 vs. 5.3 mo; P=0.0001).

One of the important trials that Dr Peters highlighted in her presentation was the IPSOS trial, which was designed to compare outcomes with the use of an immuno-oncology (IO) agent, atezolizumab relative to single agent chemotherapy with investigator’s choice of vinorelbine or gemcitabine. Importantly, this trial was designed to assess outcomes in a population of patients with Stage III or IV NSCLC who would ordinarily not be candidates for preferred therapy with platinum agents because their performance status (PS) was poor (i.e., ECOG PS 2 or 3), or because they were 70 years of age or above with substantive comorbidities that precluded the use of a platinum agent. Patients were also eligible for the trial if they had treated asymptomatic brain metastases.

The primary endpoint of the trial was OS, and some of the important secondary endpoints included progression-free survival, overall response rate, and duration of response. Other endpoints included safety and several patient-reported quality of life type outcomes. In describing the baseline characteristics in the trial Dr Peters emphasized that “these are patients you see in your practice every day”, noting more than 70% were above age 70, approximately 30% were age 80 or above, and approximately 80% of the patients had a PS of 2 or 3. She also emphasized a somewhat higher representation of squamous histology (>40%) in the study relative to non-squamous (~57%) and a distribution of PD-L1 expression which was as expected. Overall, she noted that the elderly population and high-performance status enrollment in the trial was particularly relevant for everyday practice.

In terms of survival results, there was some worry during the initial time points, as there was, for some patients, a very rapid progression and death, however, by 12 months, there was a clear separation in the survival curves (43.7% versus 38.6%), and by 24 months, this had increased to 24.3% versus 12.4% for patients in the atezolizumab and chemotherapy groups, respectively, yielding a median OS of 10.3 and 9.2 months, respectively, and a hazard ratio (HR) of 0.78 (P=0.028). Interestingly, atezolizumab was beneficial over chemotherapy across all patient subgroups, irrespective of PD-L1 status and histology, with the possible exception of patients over 80 years of age, for whom the HR was close to 1.0 (HR=0.97). Dr Peters emphasized there was also a clear benefit in terms of response rate with atezolizumab (16.9%) relative to chemotherapy (7.9%) mainly related to partial responses, and duration of response was 14.0 months versus 7.8 months, respectively.

In terms of the more modest efficacy observed in patients over 80 years, Dr Peters noted the substantively lower incidence of Grade 3 and 4 adverse events with atezolizumab versus chemotherapy (16.3% vs 33.3%) and Grade 5 treatment related mortality events (1% vs. 2.7%) which, she suggested, makes atezolizumab a more attractive choice for this patient population. Moreover, there was no unexpected toxicity with atezolizumab in these patients. Lastly, she emphasized that while there was no appreciable impact of atezolizumab on patient-reported quality of life outcomes, there was, as expected, a clear detrimental impact of using chemotherapy in this very frail population. In closing, Dr Peters noted that IPSOS was an especially important trial, as it suggests the immunotherapy treatment option as being a viable alternative to chemotherapy for an especially frail population of patients whom she very commonly encounters: “I think I see one or two of these patients every week…”

See more from the 2022 ESMO Florida Conference here.

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