Association of Age with Efficacy of Immunotherapy in Metastatic Melanoma.
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ABSTRACT:
SUBMITTER: Jain V
PROVIDER: S-EPMC7011618 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Publications
Association of Age with Efficacy of Immunotherapy in Metastatic Melanoma.
Jain Varsha V Hwang Wei-Ting WT Venigalla Sriram S Nead Kevin T KT Lukens John N JN Mitchell Tara C TC Shabason Jacob E JE
The oncologist 20191029 2
Management of melanoma has been revolutionized by the use of immune checkpoint inhibitors. Immune system changes associated with aging may affect the efficacy of immune-based therapies. Using the National Cancer Database, we evaluated the impact of age on the receipt and efficacy of modern immunotherapies in patients with metastatic melanoma. We identified 11,944 patients from 2011-2015, of whom 25% received immunotherapy. Older (≥60 years), compared with younger, patients were less likely to re ...[more]
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Project description:Harnessing the immune system to attack cancer cells has represented a holy grail for greater than 100years. While prospects of tumor-selective durable immune based therapies have provided small clinical signals for many decades, recent years have demonstrated a virtual explosion in progress. Melanoma has led the field of cancers in which immunotherapy has produced major clinical inroads. The most significant and impactful immunotherapies for melanoma utilize immune checkpoint inhibition to stimulate T cell mediated tumor killing. The major targets of checkpoint blockade have thus far been CTLA4 and PD1, two key receptors for central and peripheral immune tolerance. This review discusses current understanding of how these checkpoint blockade therapeutics have led to major clinical responses in patients with advanced melanoma. It is likely that we are poised to see significantly greater anti-cancer immunotherapy efficacy, both in improving response rates and durability for melanoma, and for other less immunogenic malignancies.
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Project description:ImportanceStrides to improve survival in metastatic melanoma have been made with the use of immunotherapeutic agents in the form of immune checkpoint inhibitors.ObjectiveTo examine the factors associated with immunotherapy receipt in patients with metastatic melanoma in the era of immune checkpoint inhibitors and the Patient Protection and Affordable Care Act.Design, setting, and participantsThis cohort study used data on 9882 patients with metastatic melanoma diagnosed from January 1, 2013, to December 31, 2016, from the National Cancer Database. Patients who did not have documentation regarding immunotherapy receipt were excluded. Data analysis was performed from July 1, 2019, to December 15, 2019.ExposureReceipt of immunotherapy.Main outcomes and measuresThe primary outcome was the association of receipt of immunotherapy as first-line therapy with sociodemographic factors. The secondary outcome was overall survival by receipt of immunotherapy.ResultsA total of 9512 patients (mean [SD] age, 65.1 [14.4] years; 6481 [68.1%] male; 9217 [96.9%] White) met the criteria for treatment analysis. A total of 3428 (36.0%) received immunotherapy, and 6084 (64.0%) did not. Increasing age (odds ratio [OR], 0.98; 95% CI, 0.97-0.98; P < .001) and increasing Charlson-Deyo comorbidity index (OR, 0.86; 95% CI, 0.80-0.92; P < .001) were associated with lower odds of receiving immunotherapy on regression analysis. Diagnosis in Medicaid expansion states (OR, 1.16; 95% CI, 1.05-1.27; P = .003), treatment at an academic or integrated cancer network program (OR, 1.59; 95% CI, 1.45-1.75; P < .001), and residence within the highest quartile of high school graduation rate zip code area (OR, 1.31; 95% CI, 1.09-1.56; P = .003) were associated with an increased likelihood of receiving immunotherapy. Median overall survival was 10.1 months (95% CI, 9.6-10.6 months) among all patients. Patients who received first-line immunotherapy had a median overall survival of 18.4 months (95% CI, 16.6-20.1 months) compared with 7.5 months (95% CI, 7.0-7.9 months) (P < .001) among patients who did not.Conclusions and relevanceIn this cohort study, patients who received immunotherapy for metastatic melanoma had improved overall survival. Residence in Medicaid expansion states, younger age, low comorbidity index, care at academic medical centers or integrated network cancer programs, and residence in zip codes within the highest quartile of high school graduation were associated with an increased likelihood of receiving immunotherapy. Recognizing sociodemographic associations with treatment receipt is important to identify potential barriers to treatment.
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Project description:Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody-drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells. As such, this review aims to highlight the potential clinical benefits of various armed antibody-based immunotherapies, including PDT, as alternative approaches for the treatment of metastatic melanoma.
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