Could these drugs be a cure for lung cancer?
You may have noticed an uptick in the advertising of two new immunotherapy drugs, Optivo® (nivolumab) and Keytruda® (pembrolizumab), which are changing the conversation about treatment of metastatic non-small cell lung cancer. That’s because for the first time in years, these drugs are showing promise in extending life in patients with this notoriously hard to treat and often fatal disease.
Immunotherapy is the new frontier in cancer care, according to Cape Cod Hospital medical oncologist Jennifer Crook, MD.
“It’s a whole different way of looking at cancer treatment,” she said. “We now have four different immunotherapy drugs that are FDA-approved for nine different cancer diseases, which is amazing. When have we ever had a drug that worked in lung cancer, as well as melanoma or Hodgkin’s lymphoma? This is an area of medicine that is absolutely exploding. “
Former president Jimmy Carter may be the most famous example of the potential for these drugs. Diagnosed during the summer of 2015 with metastatic melanoma that had spread to his brain and liver, Carter received Keytruda® in addition to the standard treatments for this disease. After saying good-bye to his family and friends, Carter got better. His scans reveal no cancer and he remains in remission today.
So, what is immunotherapy and how does it work? In simple terms, it stimulates the body’s own immune response to kill the cancer.
“From a baseline point of view, what immunotherapy is trying to do is to activate the immune system and prime the T-cells to recognize cancer cells as foreign,” said Dr. Crook.
T-cells are part of the white blood cell system and are actively involved in the body’s own immune response.
Most patients tolerate immunotherapy drugs extremely well, and that’s what is most exciting to Dr. Crook.
“These drugs work in a large number of people, who live their lives while they are on them. They feel well, they are active, they aren’t suffering from the fatigue and hair loss and all of the things that are more typical of traditional chemotherapy,” she said. “This is changing the discussions that we are having with our patients about expected prognosis.”
Good News For Lung Cancer Patients
Lung cancer is one of the most commonly diagnosed cancers in the U.S. for both men and women. The American Cancer Society estimates 234,030 Americans will be newly diagnosed this year.
It is also one of the most deadly. It is predicted that 154,050 people in the U.S. will lose their lives to the disease this year. One third of all lung cancers are already stage three or higher when diagnosed for the first time, according to the American Lung Association.
Prognosis for disease-free survival from lung cancer isn’t great, especially when it is locally advanced or metastatic. The current standard of care is surgery (when possible) and concurrent chemotherapy and radiation.
Cape Cod Hospital radiation oncologist Jeffrey Martin, MD, is most enthusiastic about the findings of the PACIFIC trial, which evaluated the use of Imfinzi® (durvalumab) to treat people with inoperable stage three non-small cell lung cancer that was locally advanced, but not metastatic.
“Most of the research to date has been in the metastatic setting, which is what usually happens. But, this is the first one that it is getting into the locally advanced, but potentially curative setting,” said Dr. Martin. “So that’s where there’s a lot of excitement here.”
According to the study, published in the November 16, 2017, edition of The New England Journal of Medicine, patients who were treated with Imfinzi® had a big difference in their progression-free survival, and there was also a decrease in the overall number of deaths. The effect was so profound the researchers reported it early, said Dr. Martin.
The study, funded by pharmaceutical giant AstraZeneca, included 713 participants at 253 centers across 23 countries. Four hundred and seventy-three people received the study drug, while the remainder received a placebo. The median age was 64 years old, the majority were men (70.1 percent) and most were current or former smokers (91.0 percent).
Key findings of the PACIFIC trial:
- Patients who received the study drug lived without additional disease three times as long – on average 16.8 months versus 5.6 months for the placebo group.
- The 12-month progression-free survival rate was 55.9 percent versus 35.3 percent.
- The 18-month progression-free survival rate was 44.2 percent versus 27.0 percent.
- In patients who have never smoked, the median time to death, or distant metastasis, was almost twice as long with the study drug (23.2 months versus 14.6 months).
- The frequency of new lesions was 20.4 percent with the study drug versus 32.1 percent, with a lower incidence of new brain metastasis (5.5 percent versus 11.0 percent).
The FDA has already approved Imfinzi® for use in the general patient population and it has been added to the standard protocol for care.
“We have started using this drug already,” said Dr. Martin.
Patients with poorly controlled autoimmune diseases may be ineligible. Also, those whose tumors do not contain the EGFR genetic mutation (epidermal growth factor receptor) or where the protein known as PDL (programmed death ligand) has a low percentage of expression may also be exempt, said Dr. Crook.
An Outright Cure?
Not yet. Just like traditional chemotherapies, long-term use of immunotherapy almost always results in the development of resistance. But, these drugs are effective for much longer that traditional chemotherapy, which typically only work for about three to six months.
And with more and more of them coming on the market, the potential impact is hopeful.
“We continue to learn more about these immunotherapy treatments and how they can be combined with other modalities, such as radiation therapy. The hope is that we will be able to improve survival and potentially even cure patients that were previously thought to be incurable,” said Dr. Martin.