Given disconcerting low success rates overall in immunotherapy, some leading oncologists are calling for greater scientific rigor in clinical trial design.
Immunotherapy has ushered in a new golden age of cancer treatment. Checkpoint inhibitors have offered new hope in the battling a variety of cancers. However, only about 20% of patients who receive these agents are benefitting. It is believed combining checkpoint inhibitors with immune modulators may help boost the number of patients who benefit. However, these new promising approaches to treating cancer have triggered an avalanche of trials, leaving some to question if there are too many open clinical trials.
A recent report indicates there are more than 1,100 studies involving checkpoint inhibitor–based immunotherapy. There is growing concern, however, regarding whether this cornucopia of clinical trials represents the best approach towards identifying optimal regimens for a variety of cancer patient populations. “We need to look at what factors may be involved when a large percentage of patients are not responding. We need to use precision medicine–guided therapy,” said Roy Herbst, MD, PhD, from Yale Cancer Center and Smilow Cancer Hospital, New Haven, Conn.
Herbst said the field of oncology has changed significantly in the past 5 years, with new oncology trials starting every week. Concerns have been raised that the existence of so many uncontrolled trials may be counterproductive due to difficulty in achieving enrollment goals, and in some cases due to potential drug profits outweighing scientific rigor.
Herbst said there needs to be combinations or sequences of these agents “that are smart,” and emphasized that the tumor microenvironment is more important than previously recognized. “We are looking at both now. The regulatory cells and the microphages,” Herbst told Cancer Network. “We are learning from each study.”
Justin E. Bekelman, MD, from the Abramson Cancer Center at the University of Pennsylvania Perelman School of Medicine, Philadelphia, said what is needed are trials that demonstrate efficacy and ultimately effectiveness in the real world. “While we cannot and may not need to randomize every question for targeted or precision therapies, we do need impactful and efficient trial designs that demonstrate whether these therapies achieve the goal of highly effective cancer treatment with meaningful clinical benefit,” Bekelman told Cancer Network.
Igor Puzanov, MD, from Roswell Park Comprehensive Cancer Center, Buffalo, said the number of new trials is not surprising. “You have to combine things is what we are starting to understand,” he said. “We need more science. We don’t know if this is good for the patients or bad for the patients.”
Puzanov added that, every so often, a researcher will luck out with a special combination. It may be something with a broad range of activity, and the investigators will not even know what mechanisms are involved. He believes that, while there are some potential benefits to having so many trials, there needs to be a way better distinguish patients who are nonresponders from those who are exceptional responders.
“It is going to be a challenge to go to phase II and phase III because there will be a problem getting patients. A lot of the patients will not be interested in randomization when they can get [the immunotherapy] without randomization [in an open trial],” Puzanov told Cancer Network.
Dr. David Gerber, from UT Southwestern Medical Center’s Simmons Cancer Center, Dallas, Tx., agrees with Puzanov. He said that some immediate changes are needed in the approach to trial development. “There are literally hundreds of immunotherapy trials currently underway. Some of these trials lack strong biologic rationale and have suboptimal designs. These treatments are costly, potentially toxic, and provide durable benefits to only a minority of patients. We therefore need to approach the design of immunotherapy clinical trials with rigor and justification,” Gerber told Cancer Network.