The annual meeting of the American Association for Cancer Research held in Philadelphia was the host of two presentations on immune checkpoint inhibitors – drugs that offer promise in battling severe melanoma.
Their ability of supercharging the body’s immune system by pushing it to destroy cancer cells was tested in two clinical trials conducted by Dr. Suzanne Topalian, head of the Melanoma Program at Johns Hopkins’ Sidney Kimmel Comprehensive Cancer Center in Baltimore.
Yervoy (ipilimumab) is an immune-boosting drug that used to have the best chances of fighting melanoma, but one trial revealed that Keytruda (pembrolizumab), another immune-focused inhibitor, has offered an even better performance. The other trial proved that Yervoy was not as efficient on its own as a mix of two different types of immune checkpoint inhibitors, to which patients responded better than expected.
Both studies were published in the same issue of the New England Journal of Medicine. Until now, melanoma was considered a fatal disease, with little chance of fighting it. However, according to Dr. Gary Schwartz, director of the department of Hematology/Oncology at Columbia University Medical Center in New York City, the new treatments offer more than 9 to 11 months to live.
Instead, melanoma patients are now offered 5 to 10 years of living with metastatic disease, a feat which is unheard of. Schwartz believes these immune-boosting drugs are potential treatments against many other forms of cancer.
Making breakthroughs for melanoma patients
Yervoy received authorization from the U.S. Food and Drug Administration back in 2011. The drug is set to activate and deactivate an immune system “switch” dubbed as CTLA4 – the one responsible with the body’s immune cells that’s making sure they don’t get out of hand.
CTLA4 is one of the controls that cancers use in order to remain under radar and avoid destruction by the body’s immune system. Apparently, these molecules provide a shield around tumors so the immune cells cannot get to it, preventing destruction.
There’s another drug targeting a more cancer-specific control called PD1 that has also received FDA authorization, and it represents the last attack on tumors, when Yervoy treatment is inefficient.
Keytruda proved to be the best anti-PD1 drug, with the mildest side effects in the trial involving more than 800 advanced melanoma patients from 16 countries. One-third was administered Yervoy and the remaining two-thirds got Keytruda.
Both the six months follow up and the one year follow up showed better progression-free survival rates for Keytruda: 46 percent and 74 percent, respectively. Yervoy showed lower rates of patients whose cancer tumors have not grown: 26 percent after six months of treatment and 58 percent after a year. Keytruda also won in the category of less patients affected by side effects: 12 percent, in contrast with 20 percent with Yervoy.
The best results, however, were provided by the second clinical trial, which focused on administering a combination of two different types of immune checkpoint inhibitors. But not only did results increased, so did the risk of experiencing side effects, which made researchers weary of recommending this course of treatment.
Clinical trials offer hope of more than a few months to live
More than 140 patients were part of the second trial, all with advanced melanoma. One third was put on Yervoy, while the remaining two-thirds received a combo therapy: Yervoy and Opdivo (nivolumab).
An astonishing number of 61 percent of patients responded well to the mixed treatment, in contrast with only 11 percent that reacted to Yervoy being administered on its own. Chief trial investigator, Dr. Jedd Wolchok, head of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York City, said that even though we have a seemingly better course of treatment that seems to be working, side effects should be taken into consideration.
More than half of the patients on the combination therapy experienced moderate to severe side effects – instead of attacking solely the cancer, these treatments also target the major organs of the body. Schwartz explained that this causes some serious organ damage, albeit temporary, and in a reduced number of cases, even organ failure.
Besides side effects, the new cancer drugs have another downside: the costly price can easily reach $100,000 a year. However, this is only the beginning and treatments will continue to improve and become more accessible.
Advanced melanoma was considered virtually untreatable, so this is a major discovery, allowing patients more than just a few more months to live. Some patients have even experienced complete remission, and others managed to stabilize their cancers.
Image Source: Red Orbit
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