Effectiveness and Safety of First-Line Pembrolizumab in Older Adults with PD-L1 Positive Non-Small Cell Lung Cancer: A Retrospective Cohort Study of the Alberta Immunotherapy Database.

Heidi A I Grosjean,Shiying Kong,D Gwyn Bebb,Daniel Y C Heng,Igor Stukalin,Aliyah Pabani,Quincy Chu,Samantha Dolter,Siddhartha Goutam,Daniel E Meyers,Winson Y Cheung,Philip Q Ding,Don G Morris

doi:10.3390/curroncol28050357

Heidi A I Grosjean, Shiying Kong + Show 11 more

Open Access

https://doi.org/10.3390/curroncol28050357

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Abstract

The emergence of immunotherapy revolutionized the treatment of non-small-cell-lung cancer (NSCLC), with multiple landmark clinical trials establishing the efficacy of these agents. However, many patients who receive immunotherapy in clinical practice would be considered clinical trial ineligible. One such population that is often under-represented in clinical trials is older adults. In the current study, we evaluated clinical and safety outcomes in this population. Overall, older adults (>70 years of age) and younger adults had comparable clinical outcomes with an equivalent objective response rate (ORR), time to treatment failure (TTF), and median overall survival (p = 0.67, p = 0.98, and p = 0.91, respectively). Furthermore, the safety outcomes were equivalent between the cohorts with similar rates of immune-related adverse events (irAEs), irAE-related hospitalizations, and all-cause hospitalization (p = 0.99, p = 0.63, and p = 0.74, respectively). While older age was not found to impact overall survival, multivariant analysis revealed that a poor Eastern Cooperative Oncology Group (ECOG) status, low body-mass-index (BMI), and poor/intermediate lung immune prognostic index (LIPI) were all associated with worse survival. In conclusion, age does not impact the efficacy or safety of pembrolizumab in NSCLC, and therefore advanced age should not be a deterrent for treating these patients with pembrolizumab. Physicians and care providers can thus focus on other factors that may influence therapeutic outcomes.

Highlights

In 2018, lung cancer was the leading cause of cancer death worldwide, and represented 11.6% of all new cancer cases globally [1]
We found that Eastern Cooperative Oncology Group (ECOG) ≥ 2, the presence of liver metastases, BMI < 30, an elevated platelet−leukocyte ratio, intermediate/poor lung immune prognostic index (LIPI), low albumin, and low hemoglobin had a signal of association with a worse overall survival (OS) (Supplemental Table S3)
Our multivariable analysis indicated that ECOG ≥ 2, BMI < 30, intermediate/poor LIPI, hypoalbuminemia, and anemia were all associated with worse survival outcomes

Summary

Introduction

In 2018, lung cancer was the leading cause of cancer death worldwide, and represented 11.6% of all new cancer cases globally [1]. The 5-year follow-up data from the KEYNOTE-024 clinical trial showed a median OS (overall survival) of 26.3 months for Programmed Death-Ligand 1 (PD-L1) positive NSCLC patients treated with first-line pembrolizumab, with almost a third of the pembrolizumab group still alive at the 5-year mark [4]. While these clinical trials provide valuable information, the cohorts selected often do not accurately represent patients in a real-world setting. In clinical practice, many NSCLC patients that would be considered clinical trial ineligible receive immunotherapy [6], and there is limited information on the effectiveness of pembrolizumab in these real-world cohorts

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