EA5221 – A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult with Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study

The study chair for this trial is Megan A. Baumgart, MD (University of Rochester, Wilmot Cancer Institute) and the study co-chairs are Balazs Halmos, MD (Montefiore Einstein Comprehensive Cancer Center) and Carolyn J. Presley, MD, MHS (The Ohio State University Comprehensive Cancer Center). Dr. Presley is Co-Chair of the Geriatric Oncology Working Group, part of the ECOG-ACRIN Health Equity Committee.

Lung cancer is the leading cause of cancer death in the United States and disproportionately affects older adults: 70% of all cases are diagnosed in patients ages 65 or older. Additionally, 40% of patients diagnosed with advanced disease have moderate to substantial impairment in functional status at baseline. However, vulnerable older adults are severely underrepresented in clinical trials and were largely excluded from recent pivotal studies evaluating immunotherapy—studies that have changed the landscape of advanced non-small cell lung cancer (NSCLC) management and may be of great benefit to this patient population. 

In general, immunotherapy with pembrolizumab has become the standard first-line treatment, or part of the standard first-line treatment, for most patients with advanced NSCLC. Recent studies have shown that both chemotherapy plus immunotherapy as well as single-agent immunotherapy yield better results for patients than chemotherapy alone. However, concern remains that most of the benefit of single-agent immunotherapy is limited to the patient population with high levels of PD-L1 expression. It is not clear what the optimal therapy should be between immunotherapy versus chemo-immunotherapy for patients with low PD-L1 expression, as measured by a Tumor Proportion Score (TPS) of 1-49%. The optimal treatment for older adults in this population is also poorly defined.

EA5221/ACHIEVE is a randomized phase 3 trial to evaluate the clinical outcomes of vulnerable older adults with advanced NSCLC who are treated with pembrolizumab alone compared to those treated with pembrolizumab plus chemotherapy. At the time of Step 1 (registration), investigators will select the chemotherapy regimen they believe is most appropriate for the patient, should the patient be randomized to the chemo-immunotherapy arm.

After registration, patients will undergo an abbreviated baseline geriatric assessment (GA), which includes a functional, nutrition, cognition, and quality of life evaluation. All patients will then move on to Step 2 (randomization). The baseline GA results will be provided to investigators prior to the final chemotherapy selection so that they can modify their initial plan, if needed. The GA will also provide recommendations for supportive care based on patient scores.

The study’s primary endpoint is overall survival. Additional endpoints include progression-free survival, tolerability as measured by toxicity, the association between geriatric assessment findings and clinical outcomes, and evaluation of quality-of-life measures for each treatment arm.

To be eligible for this study, patients must be age 70 or older and have NSCLC with a PD-L1 TPS range of 1-49%. Patients must have stage IIIB, IIIC, or IV disease and not be candidates for combined chemo-radiation. Patients must not have been previously treated for metastatic disease.

ACHIEVE is the second clinical trial initiated by the ECOG-ACRIN Cancer Research Group’s Geriatric Oncology Working Group, following the GIANT study (EA2186).  

Learn more about EA5221/ACHIEVE at ecog-acrin.org.