Patients With Metastatic or Unresectable Melanoma: Exploration of Pembrolizumab Treatment Outcomes Across Adult Cohorts
Introduction: The risk for melanoma increases as people age and due to an increasingly older population, more older adults are being diagnosed with melanoma in New Zealand. Pembrolizumab, a highly selective monoclonal antibody medication is the first-line treatment for metastatic and unresectable melanoma. While pembrolizumab is generally well-tolerated, immune-related adverse events and systemic toxicities threaten the completion of treatment for some patients. This research investigated whether there are any differences in outcomes between patients aged 50 years and under, 51-65 years, 66-80 years, and 81 years and older.
Methods: A database was provided by the Data and Analytics department of the hospital of patients who had received pembrolizumab between January 2017 to June 2021 and this was anonymised before analysis. Descriptive statistics were used to characterise the study population: gender, age, ethnicity, district health board (DHB) of enrolment, and any comorbidities. Independent T-test measured mean scores and associations between continuous variables and categorical predictors. One-way analysis of variance (ANOVA) explored associations among continuous variables and two or more categories, with Tukey HSD post hoc testing applied to detect the influential variable(s). Chi-square analysis for independence tested relationships among categorical predictors and outcomes. Fisher’s Exact test (two-sided) was applied when cell size did not meet assumptions for chi-square analysis. Regression analyses were applied to predict categorical outcomes with two or more categories (using binary logistic regression) to test the effects of study factors on three models: (1) Response to Treatment, (2) Disease Progression, and (3) Toxicity.
Results: A total of 300 patients were included in the study. The overall treatment efficacy for pembrolizumab was 35% (n=135/300) across all age bands. The 81 years and older age group were less likely than other age groups to experience disease progression (β = -.61(.18), p < .001). However, disease progression was more likely in patients with cardiovascular comorbidity, indicating it is an important comorbidity to be aware of (β = 1.36(.38), p < .001). There were no significant differences in cardiovascular comorbidity by DHB (p = .09), or gender (p=.06). Increasing age was significantly related to higher toxicity (β = .96(.24), p < .001). However, there were no statistically significant differences for toxicity by DHB (p = .34), or gender (p = .99). By gender, age, or DHB, there were no statistically significant differences regarding the number of treatments (p values all greater than .79) or response to treatment (p values all greater than .6). There were significant associations between age and toxicity (F(3, 296) = 6.813, p < .001), with the 81 years and older age group experiencing significantly more toxicity. There were no statistically significant differences for toxicity by DHB (p = .34), or gender (p = .99). The number of comorbidities for males (M = 1.41, SD = 1.63) was significantly (p = .039) different to females (M = 1.03, SD = 1.21). These results support that comorbidity occurs more frequently as patients age and that males have more comorbidities than females. There were no differences in comorbidities and the DHB that patients attended.
Conclusion: This retrospective cohort study confirms that age is not a limiting factor in receiving pembrolizumab for metastatic or unresectable melanoma, as supported by the tumour response within patients. Older old adults (81 years and older) can benefit as much as their younger cohorts to achieve stable disease, a partial or complete response. Therefore, this means age is not an exclusion criterion for pembrolizumab. Indeed, older adults over 81 years old were less likely to suffer from disease progression than those under 50, supporting the resiliency that age brings in some circumstances. Cardiovascular comorbidity decreases the likelihood of responding to treatment and increases the likelihood of disease progression. There is a higher likelihood of toxicity experienced as people age. Gender and DHB are not significantly related to toxicity, response to treatment or number of treatments, nor specifically are diabetes or other cancer comorbidities.