Opinion articles

Wednesday, January 8, 2014

LETTERS: ‘Clinical Trials Remain Essential to Evaluate Combination Immunotherapies, and Against a Broader Range of Cancers’ (11/10/13 issue)

I am writing to salute Dr. Jedd Wolchok for his inspirational “Voices” column in the November 10 issue, and to echo his call for more clinical trials to evaluate combination immunotherapies.


As he points out, the rapid and durable responses observed in patients with melanoma and kidney cancers suggest a potential role for combination immunotherapy in treating other types of cancer, and I applaud efforts to pursue this approach more broadly. Numerous research initiatives are investigating the purported synergistic effects of combining immunotherapeutic agents with molecularly targeted therapies, PD-1 antibodies, or other checkpoint inhibitors as a means to improve outcomes and potentially individualize anticancer treatment. Other investigations are evaluating whether sequential treatment with two complementary immunotherapies may yield improvements in clinical endpoints over those seen with single-agent immunotherapy, while preserving other downstream treatment options.


While other cancer types appear to be fertile ground for investigating combination immunotherapy, much remains to be learned about this approach in advanced melanoma and kidney cancer. That is the rationale for the PROCLIVITY clinical trial program, which is investigating the use of high-dose interleukin-2 (HD IL-2) in combination with various inhibitors of BRAF, CTLA4, and tyrosine kinase in patients with metastatic melanoma or metastatic renal cell carcinoma. The PROCLIVITY investigators aim to assess whether HD IL-2-based combination therapy provides a more robust and durable response, compared with HD IL-2 monotherapy, and to identify the optimal sequencing of individual agents in combination regimens.


Findings from these and other trials may help refine the administration of combination immunotherapy as a means to improve treatment outcomes across various cancer types. To paraphrase Dr. Wolchok and his patient, Mary Elizabeth Williams, we can and should be making these malignancies more treatable for all cancer patients.


Joseph I. Clark, MD, FACP

Professor of Medicine

Loyola University Stritch School of Medicine

Maywood, Illinois