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Abstract
Background Elderly patients are often underrepresented in clinical trials owing to exclusionary comorbidities which are more common with age, frailty and a poorer overall performance status.1, 2 Chemotherapy is poorly tolerated in elderly comorbid advanced cutaneous squamous-cell carcinoma (CSCC) patients however little is known on the efficacy and tolerability of immunotherapy in this population. To our knowledge this is the largest dedicated report on a cohort of elderly trial-ineligible patients with advanced CSCC treated with immunotherapy to date. The cemiplimab registrational study, which established immunotherapy as the standard of care for advanced CSCC, enrolled patients with a median age of 71 years (73% over 65 years, n=43).3
Methods This study was a single-centre retrospective review of elderly patients (aged 70 years or more) with locally advanced (not amenable to curative surgery or radiotherapy) or metastatic CSCC who were deemed ineligible for clinical trials and received immunotherapy via a compassionate access scheme between August 2017 and January 2022. Patient demographics, tumor characteristics, treatment history and toxicity data were collected. Disease control rates (DCR), overall response rates (ORR), median overall survival (OS), disease specific survival (DSS) and median progression-free survival (PFS) were assessed. Response assessments for patients with imaging available post commencement of immunotherapy were performed as per RECIST1.1 and/or PERCIST1.0 criteria as appropriate. Kaplan-Meier analysis was performed and descriptive statistics were used.
Results 53 patients ≥ 70 years old receiving immunotherapy were analyzed. Median age was 81 years (range 70-96); 81% were male; 34% immunocompromised; and 34% ECOG 2 or higher. 15% patients had distant metastatic disease (see table 1). All patients were treatment naïve. Average Charlson Comorbidity Index including and excluding solid organ cancer was 9 and 5 respectively. 33% developed an immune-related adverse event (IRAE) but only 2 patients experienced a grade 3 IRAE and 6 patients discontinued due to toxicity with no treatment related deaths. 34 patients were followed with FDG-PET with an ORR of 59% and DCR of 76%. Response assessments are summarised in table 2. With a median follow up of 7.9 months, median OS was 20.5 months (95%CI 11-NA) (Figure 1) and median DSS 25.6 months (95%CI 20.5-NA) (Figure 2).
Conclusions Immunotherapy is effective and well tolerated among elderly trial-ineligible patients with advanced CSCC with no increase in toxicity and a comparable efficacy to what has been demonstrated in current clinical trials.
References
Denson AC, Mahipal A. Participation of the elderly population in clinical trials: barriers and solutions. Cancer Control. 2014;21(3):209–14.
Sedrak MS, Mohile SG, Sun V, Sun CL, Chen BT, Li D, et al. Barriers to clinical trial enrollment of older adults with cancer: A qualitative study of the perceptions of community and academic oncologists. J Geriatr Oncol. 2020;11(2):327–34.
Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2018;379(4):341–51.
Ethics Approval The study was approved by the Peter MacCallum Cancer Centre Human Research and Ethics Committee HREC/76580/PMCC (21/124).
Consent The study was approved by the Peter MacCallum Cancer Centre Human Research and Ethics Committee HREC/76580/PMCC (21/124) with a waiver of consent granted.
Basic Demographics
Response Assessments
Overall Survival
Disease Specific Survival