Interventional oncology should identify “unmet immunotherapy needs”

Daniel Sze

Daniel Sze, speaking at the ninth annual Symposium on Clinical Interventional Oncology (CIO; 4–5 February 2017, Hollywood, USA), noted that immunotherapy is a “huge opportunity” for interventional oncology.

Sze, professor of Radiology, Stanford University, USA, was speaking on the potential role of immunotherapy in interventional radiology. “The immune system is the natural defense against cancer and plays a role in surveillance, recognition, attack and vigilance. It is important to understand at least the following checkpoints: cytotoxic T lymphocyte-associated protein 4 (CTLA-4); programmed cell death protein 1 (PD-1); and its ligand (PD-L1),” he said.

Immunotherapy involves stimulating the cancer patient’s immune system so that it can robustly fight the disease. Sze used the analogy of a military defense strategy to counter insurgencies to elaborate on the rationale behind immunotherapy: “Instead of sending in more US marines, teach the local militia to expel the insurgents,” he said alluding to how immunotherapy works.

As reported in the June 2016 cover story in Interventional News, experts now believe that there could be a time when interventional radiologists no longer perform procedures to destroy tumour tissue alone—they might be ablating or embolizing to provoke the patient’s immune system to powerfully destroy cancer cells.

Sze then drew attention to a variety of immunotherapy agents such as ipilimumab, pembrolizumab, nivolumab, and atezolizumab. Ipilimumab was US FDA approved in 2011 and saw US$1 billion sales in 2015. Indicated for late stage melanoma, or as an adjuvant therapy, this monoclonal antibody may result in autoimmune toxicity and costs around US$150,000 for four infusions. PD-1/PD-L1 inhibitors pembrolizumab and nivolumab were approved in 2014 and have both gone on to see huge sales. Pembrolizumab has US FDA indication for late stage melanoma and added indications for non-small cell lung carcinoma (NSCLC) with overexpression of PD-L1 and for head and neck squamous cell carcinoma. Nivolumab is approved for melanoma, NSCLC, renal cell carcinoma, Hodgkin lymphoma, and urothelial carcinoma.

Sze emphasised the high cost of immunotherapy agents and noted that health agencies in some countries had halted their routine use in the healthcare system on the basis that they have not been shown to be cost-effective. In addition, systemic administration may result in life-threatening autoimmune toxicity, leading to warnings from the US FDA, he noted.

There are also other types of immunotherapies such as cell-based therapy which involves the introduction of new components of the immune system which have been engineered or manipulated outside of the body, taught to recognise cancer, and reintroduced into the patient. In addition, oncolytic immunotherapy uses engineered viruses to selectively infect cancer cells. Infected cells undergo lysis, releasing antigens, and the ensuing stimulation of the immune system promotes attacking of cancers throughout the body.

“Sorafenib taught medical oncologists to keep their patients, avoid referral to tertiary care, and avoid referral to interventional radiology. We cannot allow systemic immunotherapies to repeat this history. We must re-establish interventional radiology as a key player in cancer care. This will not be handed to us—we must generate the data,” urged Sze.

“Interventional radiology must identify the unmet needs within immunotherapy: many therapies are systemically toxic and some cannot penetrate tumour microenvironments. The response rates are still low and cancers are a biochemical moving target. We must devise interventional radiology solutions and administer these locoregionally. We must disrupt tumours and uncloak antigens. We must select patients based on tumour genetics and track changes in biochemistry,” he concluded.