Jedd D. Wolchok, MD, PhD
Immunotherapy agents are delivering impressive results in a broad range of tumor types, reinforcing the excitement in research and investment circles for anticancer strategies that actively harness the immune system, according to experts analyzing an avalanche of data presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
The modality once again emerged as a highlight of the annual meeting, even though many of the findings reported this year stemmed from early-stage clinical studies.
Several key trends are unfolding:
Checkpoint blockade agents are the leading form of immunotherapy under exploration, particularly antibodies targeting PD-1 or its ligand PD-L1, where results were reported in melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and head and neck cancer (Table)
Adoptive T-cell therapy (ACT) is generating much interest, as evidenced by noteworthy results from a small cervical cancer study.1 Pharmaceutical investors have been channeling tens of millions of dollars into research involving various experimental ACT approaches in recent months
Combination studies that pair checkpoint agents with each other, with other forms of immunotherapy, and with targeted therapies are expected to become a main focus of immunotherapy research. ASCO highlights in this category included two melanoma studies: one that paired the anti-CTLA-4 antibody ipilimumab (Yervoy) with the anti-PD-1 agent nivolumab,2 and another that combined the oncolytic virus therapy T-VEC with ipilimumab.3
Leading immunotherapy researcher Jedd D. Wolchok, MD, PhD, summarized the broad trends emerging from the ASCO meeting in an interview with OncologyLive
. Wolchok, chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York City, helped lead the clinical trial that led to the FDA’s approval of ipilimumab in metastatic melanoma three years ago. He also is among this year’s Giants of Cancer Care™ award winners.
“I see a lot of enthusiasm for immunotherapy in new diseases, bladder cancer being the example that I think was most recognized at ASCO this year in terms of new disease targets,” said Wolchok.“I see the checkpoint modulators having roles by themselves as well as in combination with each other. I also see the checkpoint blocking antibodies having a role when combined with other more conventional anticancer therapies—targeted therapies, radiation, chemotherapy—and seeing those trials mature, I think, is very important.”
Wolchok noted that researchers also are turning their attention toward checkpoints that activate the immune system, which includes his laboratory’s focus on OX40 and GITR.
“We also recognize that there is another part to immunotherapy— not just blocking the brakes, but also stepping on the gas by developing agonist agents for costimulatory pathways,” said Wolchok. “So we now have multiple tools available to try and modulate the immune response in the most potent way possible.”
Although Wolchok has concentrated on checkpoint agents, he feels there is room for many immunotherapy approaches in the anticancer armamentarium. “I don’t think we should say it is only going to be about checkpoint inhibitors, or only going to be about T cells, or only about those two things. There is a lot that we’ve learned about the need for additional immune-modulating agents, so we shouldn’t think exclusively about those two [approaches]. “We have to think more widely rather than more narrowly,” he said.
$9 Billion Market Forecast
The biopharmaceutical industry has been investing heavily in immunotherapy research, and those efforts are expected to bear fruit in the next decade.
The market for immunotherapy drugs will reach $9 billion in the United States, Western Europe, the United Kingdom, and Japan by 2022, according to the Decision Resources Group, a global healthcare analytical company.
Rachel Webster, MSc, DPhil
Checkpoint inhibitors, particularly agents that target PD-1 and its ligand PD-L1, are expected to account for most of that growth, with nearly $8 billion in sales in major markets, Decision Resources forecasts in its “Immunotherapies Pharmacor” report.4
“Clearly, immunotherapy was the highlight of the ASCO meeting. An enormous amount of data is coming out on the checkpoint inhibitors, particularly the PD1 agents and the anti-PDL-1 therapies,” said Rachel Webster, MSc, DPhil, an oncology analyst at Decision Resources. As a class, immune checkpoint agents “are demonstrating rapid, prolonged, very durable responses, and really unprecedented responses,” said Webster.