The Landscape of Cancer: Immunotherapy Shining Through
| Oct 7, 2015
Co-authored by Cory Lewis, Ph.D.
Immunotherapy is shining through in the crowded space that is oncology, over 6,000 oncology drugs are in development with more than 2,400 different mechanisms of action (MOAs). Immunotherapies have started to enter the mainstream, with many headlines touting immunotherapy as the Holy Grail of cancer treatment. The immunotherapy market includes more than 75 drugs in development for oncology. The race is now on for the next FDA-approved immunotherapy in cancer as well as expanded indications for the approved immunotherapies, Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo and Yervoy.
Kantar Health’s newly developed CancerLandscape™ platform identified eight immunotherapy drugs in Phase 3 clinical trials in the U.S., with 13 in Phase 2 and 17 in Phase 1; 41 drugs that target PD-1 alone are in various stages of development, many in preclinical development that may never make it to clinical trials. Given the positive data and recent approvals, companies are trying to expand immunotherapies to other indications. Just looking at Keytruda (Merck & Co.), Opdivo (BMS), atezolizumab (Roche), and Yervoy (BMS) more than 422 trials are currently ongoing. This equates to more than 80,350 patients participating in trials in over 60 different tumor types. Add on top of this, newer target indications that appear almost daily.
Immunotherapies could completely change treatment paradigms within a tumor. In melanoma, for example, the best option before immunotherapy was interleukin-2, which had an only 6% complete response rate1 with a very large side-effect profile. The level of unmet need was high, and Yervoy was able to reduce the risk of death by 32% in these patients. Recently, Opdivo showed an overall response rate of 32% in advanced melanoma patients and a one-year survival rate of 73%.2,3 In an indication with very few options and dismal outcomes, immunotherapy is allowing patients to live longer.
Not only are immunotherapies improving clinical outcomes, they also show the potential to affect management of cancer patients in other areas. With immunotherapies moving further up in lines of therapies and quickly becoming the go-to option over chemotherapies, what will happen to the supportive care market? Supportive care drugs used to combat nasty side effects of chemotherapy could see a shrinking market as patients move to immunotherapies with fewer (or at least different) side effects. For example, some supportive care drugs are aimed at neutropenia, but the current approved immunotherapy drugs don’t show a significant amount of neutropenia, and as immunotherapies become more ubiquitous the supportive care market for neutropenia in cancer could shrink.
- How will immunotherapies change biomarker testing? Specifically, in melanoma, immunotherapy is moving earlier within the treatment paradigm, and treatments are efficacious regardless of BRAF. Will patients still need BRAF testing? If immunotherapy becomes standard of care in first- and second-line in melanoma, where does BRAF testing fit in?
- What about histology? Immunotherapies in lung cancer seem equally effective in squamous and non-squamous subsets. If immunotherapies become the major treatment in lung cancer does it become necessary to separate the two by histology? Immunotherapy has the ability to not only completely shift a treatment paradigm within a tumor but also to affect other markets and possibly how patients are diagnosed.
Time will tell how immunotherapies will shape treatment paradigms. However, treatments that powerful have caught the eyes of most companies. According to an in-depth analysis using our CancerLandscape™ platform, of more than 6,000 oncology drugs in development, 77 companies have immunotherapy drugs in their pipelines. Not only is the number of companies with immunotherapy drugs growing but so is the number of clinical trials with existing immunotherapies. Keeping track of who owns which drug and in which indication has become a difficult task with what seems to be a different licensing deal or acquisition every day as companies jockey to have the most promising immuno-oncology drug.
CTLA4 and PD-1 have been shown to work as targets in several indications. Now we are waiting to see what other indications these targets will work in. The science predicts there may only be a few (those tumors with high tumor burden), but we will have to wait on the data from clinical trials to see if this holds true. Of the new targets on the horizon, what will be next: OX40, LAG-3 or second-generation immuno-oncology agents such as cyclic dinucleotides directed toward the stimulator of interferon genes receptor (STING)? These second-generation compounds provide many more possibilities to investigate and many indications to investigate them in. Agents designed to target natural killer cells and macrophages are in early stages and a new take on immunotherapy drugs in cancer. Will these be able to match the PD-1 data? It will be a fun ride in which some are sure to rise to the top while others may be geared toward niche patient populations. One thing is for sure: immunotherapy will have a long-lasting effect on oncology pipelines.
- Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000 Feb; 6 suppl (1):S11-4.
- Bristol-Myers Squibb Company. (2014). Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company.
- Bristol-Myers Squibb Company. (2015). Press release June 19. Princeton, NJ: Bristol-Myers Squibb Company.