keytruda

Image courtesy of Merck

When Edith Pelka was diagnosed with advanced non-small cell lung cancer last summer, the retired New York nurse, yoga instructor, and self-described “straight shooter” thought her life was over.

“After the surgeon told me that my tumor was inoperable, I told my husband and daughter that I have had a beautiful life, and that if this is what the universe wants, so be it,” Pelka, 67, told Healthline.

And then, she added, “I started to cry. I saw a very close friend die of lung cancer. She was miserable, and she only lasted a couple months.”

However, Pelka’s despair soon turned to hope after her doctors told her she was eligible for a promising new drug regimen.

The treatment combined standard chemotherapy with a newer drug called Keytruda, which harnesses the body’s immune system to fight the cancer.

Pelka, a warm, gutsy woman who as a child escaped with her family from Hungary when the Russians attacked in the late 1950s, told her family she had nothing to lose by trying this new treatment.

Today, less than a year later, she’s doing “fantastic,” said her oncologist, Dr. Balazs Halmos, director of thoracic and head and neck oncology at Montefiore Medical Center and Albert Einstein College of Medicine in New York City.

“Edith has responded to her treatment amazingly well and is in a nice remission,” Halmos told Healthline.

Pelka is “wintering” in Florida and enjoying the life she says was given back to her thanks to this groundbreaking treatment.

She couldn’t be happier.

“I feel very lucky. These immunotherapies are major breakthroughs, like the vaccines of the last century, like penicillin and the polio vaccine,” she said.

Immunotherapy takes center stage

Immunotherapy has been the subject of intense media attention lately.

And for good reason.

As many oncologists and cancer researchers have told Healthline, it’s slowly but clearly changing the face of cancer treatment.

But most healthcare analysts agree that the news this week from the latest Keytruda clinical trial is the most significant development in immuno-oncology to date.

Why?

Because this recent trial was for patients with lung cancer, the leading cause of cancer death in the world for men and women, according to the American Cancer Society.

Up until just a few short years ago, a diagnosis of advanced lung cancer was bleak. But now there’s real hope.

At the American Association for Cancer Research (AACR) conference in Chicago on Monday, Merck announced that in the Keynote-189 trial of Keytruda combined with chemo, the risk of death for lung cancer patients was reduced by 51 percent.

In patients with high levels of PD-L1, a biomarker in the body that Keytruda and other immune-oncology drugs target, the death risk was reduced by 58 percent.

In patients with low PD-L1 levels, the death risk was 45 percent lower.

“Our goal is to extend the lives of patients with lung cancer,” Dr. Roger M. Perlmutter, president of Merck Research Laboratories, told Healthline.

“The overall survival findings from Keynote-189 showing the risk of death was reduced by half in the Keytruda arm are really quite impressive and hence potentially of great importance to lung cancer patients.”

Oncologists and pharma industry analysts expect these trial results to generate a new standard of care for about 70,000 patients annually in the United States whose lung cancer has spread.

“Keytruda, and all the immunologics, are having a transformative effect on cancer,” said Dr. Sandip Patel, an oncologist, cancer researcher, and assistant professor of medicine at the University of California San Diego Moores Cancer Center who specializes in lung cancer, immunotherapy, and precision medicine.

“For advanced lung cancer patients to have an opportunity to be treated in their first line of therapy with these drugs is game-changing,” he said.

Patel added that just a decade ago, doctors would often consider whether it was ethical to treat advanced lung cancer patients at all because the outcomes were often so dismal and the chemo made them so sick.

“To come from that point to where we are now, it is remarkable. We have patients with advanced lung cancer who are now out five years from their treatment,” Patel said. 

Merck has company

While the latest news puts Merck in the front of the lung cancer treatment pack, there are multiple pharmaceutical companies with new immunotherapeutic and targeted treatments for the disease.

Another study whose results were announced at the conference this week revealed that Bristol-Myers Squibb’s immunotherapy drug Opdivo and its companion drug, Yervoy, worked better than chemo for delaying cancer progression in advanced lung cancer patients whose tumors have specific genetic mutations, as almost 50 percent do.

The benefit lasted on average just two months, however, and it isn’t yet known whether the drug combination improves overall survival.

Rachel Li, an associate director for Bristol-Myers Squibb in China, told Healthline that an Opdivo phase III study for lung cancer as second-line monotherapy has been completed and posted in AACR publications.

“We’re hopeful to get the approval by quarter three this year,” Li said.

Roche recently announced that its lung cancer immunotherapy Tecentriq improved survival in a study similar to the one testing Keytruda. More data is expected from that trial soon.

Roche announced last month that mixing Tecentriq with Avastin and the chemotherapy drugs carboplatin and paclitaxel boosted overall survival in first-line treatment of non-squamous non-small cell lung cancer, compared with patients who received only Avastin plus the two chemotherapies.

Keytruda, Opdivo, Yervoy, and Texentriq are all what are called checkpoint inhibitor drugs that identify and remove a cloak found on cancer cells that hides them from the body’s immune system.

On Thursday, the Food and Drug Administration (FDA) approved AstraZeneca’s lung cancer treatment Tagrisso for first-line treatment of patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor mutations.

Between 10 and 15 percent of patients in the United States and Europe and 30 to 40 percent of patients in Asia have these mutations.

The approval is based on results from the phase III Flaura trial, which were presented at the European Society of Medical Oncology 2017 Congress and published in the New England Journal of Medicine.

Is Keytruda too expensive?

Keytruda, a versatile drug that in addition to lung cancer is also indicated for classical Hodgkin’s lymphoma, skin cancer, bladder cancer and other cancers, reached $3.8 billion in sales in 2017, according to the Wall Street Journal.

As the New York Business Journals reported this week, Keytruda costs approximately $13,500 per month.

Most insurance companies are on board with Keytruda. And eligible patients can receive assistance. Merck provides its medicines and adult vaccines for free to eligible patients who don’t have prescription drug or health insurance coverage and who, without assistance, cannot afford the medicines and vaccines made by Merck.

Australia drastically cuts prices

In Australia, the government just moved to include Keytruda on its Pharmaceutical Benefits Scheme (PBS) for classical Hodgkin’s lymphoma.

This means that while patients in Australia with classical Hodgkin’s lymphoma would have paid around $200,000 AUD ($153,000 US) for each course of treatment, they’ll now pay no more than $39.50 ($30.31 US).

Hodgkin’s lymphoma is reportedly diagnosed in about 600 patients in Australia each year and classical Hodgkin’s lymphoma accounts for about 95 percent of these cases.

“A drug that was out of the reach of virtually every Australian will now be in the reach of virtually every Australian,” Health Minister Greg Hunt told the Nine Network this week.

In a press statement released by MSD, which is Merck’s name outside North America, Sharon Winton, the chief executive of Lymphoma Australia, praised the government for its decision.

“Nearly a hundred Australians with this form of lymphoma die each year, so we are thrilled that a new treatment option is now available and affordable,” she said.

“We often hear of Australians who are struggling to pay for expensive medicines or who only gain access to these medicines through a clinical trial, so it is heartening to hear this good news,” Winton added.

Keytruda had been available on the PBS for advanced melanoma but not blood cancer.

There is no organization like PBS in the United States.

The cost of other immunotherapies

It isn’t just Keytruda that seems pricey.

Opdivo can reportedly cost more than $250,000 per year when combined with another drug to treat melanoma.

Pharmaceutical companies point to the fact that it’s expensive to bring a cancer treatment from the lab to your local cancer clinic.

A report from JAMA Internal Medicine found that for 10 cancer drugs, the median cost of developing a single cancer drug was $648 million.

The median revenue after approval for such a drug was $1.6 billion.

But the Tufts Center for the Study of Drug Development came to a different conclusion.

The center examined 10 pharmaceutical companies and 106 randomly selected drugs that were first tested in human clinical trials between 1995 and 2007.

Its estimate for the true cost to develop and bring a drug to market was $2.6 billion.

Pamela Eisele, a spokesperson for Merck, told Healthline, “We share the concerns about the rising cost of health care overall — particularly when that cost is passed on to patients. Our priority is to make Keytruda accessible to all patients for whom it is appropriate, and we have patient support programs to help those who may experience challenges affording their medicine.”

Eisele said the amount that any patient pays for a medication is determined by the terms of the patient’s insurance policy or government program in which the patient participates, such as Medicare.

“Merck does not control this,” Eisele said. “We believe the value of Keytruda is appropriately reflected today. Merck is leading efforts to use biomarkers in immuno-oncology to advance personalized medicine and identify the best treatment approaches — monotherapy or combination — for each patient, to increase patients’ chance of success and enable better use of health care resources by utilizing the right treatment regimen."

Immunotherapy costs can be misleading

The drug-cost debate reached a crescendo last year with the advent of CAR T-cell immunotherapy.

CAR, or chimeric antigen receptor, involves the engineering of the patient’s own T cells to recognize and destroy cancer cells.

The treatment is showing an unprecedented number of complete remissions in blood cancers, even among sick patients who’ve exhausted all other treatment options.

Two CAR T-cell therapies are now approved by the FDA. One is Yescarta, for people with advanced large B-cell lymphoma. The other is Kymriah, for children and young adults with advanced B-cell acute lymphoblastic leukemia.

Yescarta is marketed by Gilead, which recently purchased Kite, a smaller biotech firm that developed Yescarta, for about $11 billion.

Kymriah is marketed by Novartis.

The cost of Kymriah is $475,000 per patient. Yescarta costs $373,000 per patient.

But CAR T-cell therapy, which is a one-time, one-shot treatment, is actually far less expensive that chemotherapy over the lifetime of a cancer patient, multiple sources tell Healthline.

A report by University of Colorado researchers concluded that the clinical benefits of these therapies justify their lofty price.

Researchers at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences conducted a study estimating the cost-effectiveness of approved CAR T-cell therapy.

Their report, “Chimeric Antigen Receptor T-Cell Therapy for B-Cell Cancers: Effectiveness and Value,” was conducted at the request of the non-profit Institute for Clinical and Economic Review.

The researchers compared CAR T-cell therapies to chemotherapy, taking into account patient survival, quality of life, and healthcare costs from the healthcare system’s point of view, over the lifetime of a patient receiving these therapies.

The researchers concluded that the potentially great clinical benefits of CAR T-cell therapies may justify their expensive price.

Hatim Husain, an oncologist, cancer researcher, and assistant professor of medicine at the University of California San Diego Moores Cancer Center, is focused on lung cancer and neurological oncology.

He told Healthline that the prices of these and other new medicines are something that must be addressed.

“The industry has to be more conscious about cost,” Husain said flatly.

He believes one of the things that will increase patient access to drugs and reduce costs is an expansion of the biosimilars market.

Biosimilars are drugs that are essentially the same as their patented predecessors. Many older-generation cancer treatments such as Avastin, Rituxan, and Herceptin have expired patents, which exposes them to rivals’ less costly copies.

Biotech companies are allowed to manufacture drugs that are essentially the same as the original drugs once the patent runs out, but typically at a substantially reduced cost.

Husain said the grown of biosimilars “democratizes” drug development.

“We may see some movement in the immunotherapy market toward biosimilars,” he predicted. “Biosimilars in immunotherapy is a bold step, but there may be some movement there. I don’t have a crystal ball; my gut feeling is that this will be interesting.”

Husain said that advanced technologies such as genetic diagnostics and more could have a positive impact on the cost of prescription drugs.

Husain said drug prices are a big reason why the industry needs more biomarkers.

The National Institutes of Health define a biomarker as a “characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”

Husain said more biomarkers will help the industry better understand who is responding to specific therapies and who isn’t.

“There needs to be continued biomarker explorations to figure out just who will get the most benefit from these drugs and who will not; that will definitely keep costs down,” Husain said.

Industry officials say there’s a reason for the higher prices.

“The U.S. private model healthcare system is very different than most other developed countries where prices are set through complex regulatory systems,” Merck spokesperson Pamela Eisele told Healthline.

One of the advantages of the U.S. system, she said, is that the United States has become the global leader in scientific research and medical innovation.

“That means patients in the U.S. typically gain access to innovative medicines earlier than those in other countries because the U.S. government does not restrict access through price controls.”

Both in the United States and globally, Eisele added, “We are working with a broad range of stakeholders to help develop and advance innovative financing and payment models with the objective of improving access.”

Patients enjoying their life

Meanwhile, lung cancer patients are embracing their remission.

When Sheila LeShure was diagnosed with non-small cell lung cancer four years ago, the mother of two and grandmother of five from Detroit wasn’t sure she wanted to enroll in a Keytruda clinical trial.

“I was concerned. I thought, ‘What if it doesn’t work?’,” she said. “But my husband and my doctor talked me into it.”

She’s now glad they did.

“I’m in remission. I have my life back. I can travel, I can do anything,” she said. “If people who read your story are not sure if they should enroll in a clinical trial, I say do it. Do not hesitate.”

Pelka agrees.

She likes to tell others who are diagnosed with lung cancer that while the treatment does have its share of unpleasant side effects like nausea and lack of appetite, it’s all worth it.

“In those times when you feel really, really lost, just remember that it’s not forever, just for a little while, and it’s worth it,” she said.

“At times you will say to yourself, ‘What on Earth am I doing? This is not quality of life.’ But it doesn’t last forever. When I get my chemo, there is a nice writing on the wall that says, ‘When the world tells you no more, hope whispers: Try one more time.’”