Beyond Systemic Anti-PD-1 and CTLA-4 in Advanced Melanoma - Is Intratumoral Therapy the Answer?

Marc Uemura and Adi Diab

Department of Hematology and Oncology, University of Texas-MD Anderson Cancer Center, USA
Department of Melanoma Medical Oncology, University of Texas-MD Anderson Cancer Center, USA

^*Correspondance to: Adi Diab 

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Abstract:

Since the FDA approval of ipilimumab (Yervoy®) in 2011, systemic Checkpoint Inhibitors (CPIs) targeting Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) and programmed cell protein 1 (PD-1/PD-L1) have significantly improved the overall survival for patients with a variety of cancer types, including, but not limited to, malignant melanoma, non-small cell lung cancer, urothelial cancer, renal cell carcinoma, and squamous cell cancers of the head and neck. In malignant melanoma, for example, the response rates to these new agents are much higher what was historically achievable with chemotherapy (<10%), and is approximately 15% and 30-40%, respectively, for anti-CTLA-4 and anti-PD-1/PD-L1 agents [1-4]. Despite these advances, however, the systemic CPI therapies are not a magic bullet - long-term survival, response rates and durable remission rates, especially in the refractory patient population, remains low. To overcome these limitations, a recent strategy has focused on systemically combining CTLA-4 and PD-1 targeted therapies. This combination has resulted in even higher response rates (~55% with ipilimumab plus nivolumab in malignant melanoma); however, it is also associated with a significantly higher toxicity rate (~60% grade 3/4 adverse events) and Complete Responses (CRs) remain low (~10%) [4,5]. Thus, there remains a significant unmet need to develop new immunotherapeutic strategies that results in higher response rates and improved long term clinical benefits without causing significant immune related toxicity. Our group has recently focused on the benefit of intratumoral immunotherapy as a rational strategy to overcome the clinical limitations of systemic CPI therapy in advanced melanoma. A brief description of this strategy and its rationale follows.

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Cite the Article:

Uemura M, Diab A. Beyond Systemic Anti-PD-1 and CTLA-4 in Advanced Melanoma - Is Intratumoral Therapy the Answer? Clin Oncol. 2017; 2: 1272.