Despite hype, still much to uncover about immunotherapy
- The recent successes of cancer immunotherapy, headlined by the checkpoint inhibitors already earning billions in sales, have spurred heavy investment into the space as biopharmas race to move promising candidates into later-stage development.
- At the same time, much is still not understood about why new immunotherapies produce durable responses in certain subsets of patients while others still see no effect.
- In light of this mismatch, Novartis’ head of exploratory immuno-oncology emphasized on Wednesday the continued need for exploratory clinical trials to unlock more broadly effective cancer immunotherapy.
As drugs like Opdivo (nivolumab) and Keytruda (pembrolizumab) barrel past blockbuster sales, and CAR-T treatments near markets, optimism in cancer immunotherapy is running high.
But that optimism belies the still-early nature of the field, at least in a therapeutic sense.
Speaking in Washington, D.C. Wednesday, Novartis Institutes of BioMedical Research’s (NIBR) Glenn Dranoff, underscored the amount of work left to be done in order to boost the efficacy of current agents in development.
"It is really only by the community as a whole and academia and industry pooling the shared learnings that come out of these very precise, very thoughtful and focused trials that more of the rules on how to generate an effective immune response will be uncovered," Dranoff said. "That then, in the fullness of time, will provide the blueprint for more effective treatments."
Dranoff spoke as part of a panel discussion hosted by Johns Hopkins Medicine to discuss how to improve immunotherapy.
Dranoff, who came to NIBR from the Dana-Farber Cancer Institute, noted that, despite the excitement around immuno-oncology, only about a fifth of patients could expect to see clinical benefit from such treatments.
Figuring out why certain patients are more likely to respond and discovering more markers that identify those patients will be crucial in further developing the field.
As that work progresses, many pharmas are turning to combinations as a possibly fruitful avenue, pairing checkpoint inhibitors with chemotherapy and other immunotherapies.
Merck, for example, is pushing ahead with a combination of Keytruda and chemo in lung cancer, while Bristol-Myers Squibb hopes its Opdivo/Yervoy combo can help it regain some lost momentum. Roche, AstraZeneca and others are pursuing similar strategies.
One potential problem with combination therapies, however, is cost. Stacking expensive immunotherapies means a pricier treatment regimen. This becomes even more of a problem when current science still doesn’t offer a clear-cut answer on who will benefit.
Roy Baynes, Merck Research Lab’s chief medical officer and another speaker on Wednesday’s panel, said pairing immunotherapy with chemo could be a good approach to address this.
"We know that a non-specific therapy like chemotherapy can markedly enhance the response rate in combination with, for example, an immunotherapy," Baynes explained. "Most chemotherapies today are generic. For a large number of them, costs are not all that large. So that may be a relatively simple combination approach in a group of patients who might demonstrate enhanced responses."
But, circling back to Dranoff’s point, expanding understanding of the field through continued exploratory research could also serve to mitigate cost concerns. Knowing who may or may not benefit could lead to more cost-effective treatment decisions, for example.
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