Is Chemotherapy on the Way Out?
New, less toxic cancer treatments are emerging, but don’t expect chemo to disappear anytime soon.
Immunotherapy is one type of new cancer treatment that could someday make chemotherapy a thing of the past.
When Mary Olsen received a diagnosis of chronic lymphocytic leukemia, the most common type of leukemia in adults, she wanted to try a new, targeted cancer therapy that was showing great promise in clinical trials.
But when it came time to get treatment, Olsen, 68, a retired director for early child care education from Indiana, says chemotherapy was her only option.
“I was scheduled for one treatment a month for six months,” she said. “Unfortunately, I did not have a successful experience with chemo.”
After two cycles, Olsen developed sepsis, a life-threatening illness caused by your body’s response to an infection.
While recovering in the hospital, she says her oncologist came to her room and told her, “No more chemo.”
That was just what she wanted to hear.
Olsen had now qualified for a new drug called ibrutinib (Imbruvica). It targets cancer but, unlike chemo, doesn’t generally destroy healthy cells.
“I was anxious, and I did have and still do have some side effects,” she said. “Fortunately, in the scope of things, they are minor and manageable. They don’t interfere with my daily life, and I am grateful for the benefits of Imbruvica.”
Photo courtesy of Mary Olsen
A new normal for cancer treatment
Olsen isn’t alone.
She’s one of a growing number of cancer patients who are turning away from chemotherapy and toward a new generation of cancer medicines.
While chemotherapy regimens have been the standard of care for most cancers for more than a half-century, the paradigm is slowly but steadily shifting to newer, personalized, less toxic modalities.
In chronic lymphocytic leukemia, for example, the first-line therapy historically included cytotoxic agents that can cause significant immunosuppression, second malignancies, and other serious side effects.
But decades of painstaking research have given scientists a far better understanding of chronic lymphocytic leukemia and, more broadly, the mechanisms and mutations of all types of cancer.
This research has opened new doors that are leading to better, safer medicines. But it’s only been in the past few years that patients have begun to really see and feel the fruits of this labor in the lab.
The new treatment landscape includes such targeted therapies as Imbruvica and dabrafenib (Tafinlar), which treats people with melanoma who have a mutated BRAF gene.
In addition, trastuzumab (Herceptin), which treats people with breast cancer who have the HER2 gene mutation, is also widely used.
So are afatinib (Gilotrif) and cetuximab (Erbitux), which block a substance called EGFR that helps lung and colorectal cancers grow.
Other new classes of drugs that are positively challenging the chemo status quo include checkpoint inhibitors such as Keytruda as well as immunotherapies, bispecifics, gene therapies, chimeric antigen receptor (CAR) T-cell therapies, cancer vaccines, and natural killer cell treatments.
Some of these treatments have been approved by the U.S. Food and Drug Administration (FDA), while others are in clinical trials or drug company pipelines.
The future of chemo
With the advent of so many new treatment options, it begs the question:
Is chemotherapy on the way out?
Most oncologists, scientists, and cancer industry observers interviewed for this story agreed that while it won’t happen anytime soon, the writing is now on the wall.
“Chemotherapy’s days are numbered,” said Ivor Royston, the pioneering oncologist, scientist, and entrepreneur who’s helped co-found multiple American biotechnology companies.
But he adds this won’t happen overnight.
“There are cancers for which chemotherapy is effective in some patients and even curative,” said Royston, who’s currently the CEO of Viracta, a biotech company in San Diego that’s advancing new medicines to benefit patients that have viral-associated cancers, including several types of lymphoma.
Viracta’s treatment, which is in clinical trials and showing strong early results, is a precision therapy focused on cancers harboring the genome of the Epstein-Barr virus.
Unlike standard chemo, this treatment potentially presents few if any adverse side effects.
And this is what scientists, and patients, are moving toward.
What is chemotherapy?
The term “chemotherapy” was first coined by German-Jewish physician and scientist Paul Ehrlich, who was referring to any chemical to treat any disease.
The term has essentially come to mean any cancer treatment that kills fast-growing cells — cancer cells or regular cells — or stops them from dividing.
Cancer chemotherapy was originally derived from mustard gas, a deadly chemical weapon used by the Germans in World War I.
During World War II, U.S. Navy personnel exposed to mustard gas were found to have toxic changes in the bone marrow cells that develop into blood cells.
At the time, there was no real treatment for blood cancers such as lymphoma and leukemia. Scientists reasoned that any agent that could kill off healthy cells might kill off cancerous ones, too.
Mustard gas itself wasn’t an option, but doctors came up with a chemical called nitrogen mustard.
As the American Cancer Society explains, this agent served as the model for a series of similar but more effective so-called alkylating agents that killed fast-growing cancer cells.
The darker side of chemo
The use of chemo agents has led to long-term remissions and even cures of some cancers, including Hodgkin’s lymphoma, childhood acute lymphoblastic leukemia, and testicular cancer.
No cancer experts interviewed by Healthline suggest that chemo be completely shelved.
But almost all of them agree that more than ever, there’s newer, better, and safer treatments either here or coming soon for multiple types of cancer.
Chemotherapy often brings with it a great physical and emotional cost to the patient in terms of quality of life.
The side effects of chemo — during and even sometimes after treatment — can be difficult to endure, despite the fact that drugs have been developed to reduce nausea, vomiting, diarrhea, and hair loss.
Chemo can also cause organ damage and even secondary cancers that appear later.
New treatments highlighted
Attendees at the ASH annual meeting this month in San Diego. Photo courtesy of the American Society of Hematology
At the American Society of Hematology (ASH) annual meeting earlier this month in San Diego, a number of non-chemotherapeutic treatments for blood cancers that have been effective in human clinical trials were spotlighted.
Among the drugs that most impressed the 30,000 doctors, researchers, and patient advocates who attended the conference in the field of blood cancer was Imbruvica.
In trials presented at ASH, the new drug was shown to work better than chemo for chronic lymphocytic leukemia.
Whether alone or in combination therapy, Imbruvica, which comes in pill form, was shown to be more effective and less toxic than chemotherapy in clinical trials for people over 65, the typical age group for this disease.
“It is a practice-changing medicine,” said Dr. Danelle James, MAS, head of clinical science at Pharmacyclics, a Silicon Valley-based company owned by Chicago pharmaceutical giant AbbVie that manufactures and markets Imbruvica.
James spent a decade as an assistant professor and cancer researcher at the respected University of California at San Diego Moores Cancer Center studying drugs’ effects on cancer.
She told Healthline that the compassion she felt for her patients at the San Diego facility drove her to her present job at Pharmacyclics, whose motto is “Patient-first. Science-based. Employee-driven.”
The more interaction she had with patients, the more she says she realized she could be of more immediate help bringing less toxic and more effective treatments to patients by doing research for a pharmaceutical company.
“I loved the patients and my practice, but I was able to look them in the eye and say, ‘I can do more for you if I go to work for one of the companies that have these novel agents,’” she explained.
“I told my patients that I would work to make sure this drug gets to you,” she said. “They realize now that this was a good move for me.”
Andrew Weil’s prediction
Even some of the most heralded holistic and integrative physicians recognize that some chemotherapies will survive this onslaught of new medicines.
If not for long.
Dr. Andrew Weil, a Harvard-educated physician, author, lecturer, and internationally recognized pioneer of integrative medicine, told Healthline that chemotherapy is still an integral part of oncology, but it will become obsolete and be replaced by newer treatments.
“But we’re not there yet,” Weil said, who’s the founder and director of the University of Arizona Center for Integrative Medicine and co-editor of the book “Integrative Oncology.”
“Chemotherapy targets rapidly dividing cells. For tumors with high cell division rates, including testicular cancer, many leukemias and lymphomas, chemotherapy can be highly effective, and the damage to normal tissues with high cell division rates such as skin, GI tract, bone marrow, is justified,” he said.
But the cells of many other tumors “do not divide so fast, and the harm chemo does — to the immune system, especially — is unacceptable,” he said.
In his practice, Weil says he just saw a 46-year-old man with advanced metastatic testicular cancer who’s cancer-free as a result of aggressive chemotherapy.
“His general health is now good,” Weil said.
He adds that integrative oncologists can increase the efficacy and reduce the toxicity of chemo by “timing it properly, by dietary adjustment, and by giving it along with natural products like astragalus, milk thistle, and medicinal mushrooms that protect bone marrow, liver, and other organs.”
“I would say chemo is still an important option in cancer treatment, but it will not be in the future — sooner, I hope, than later,” Weil said.
Bispecifics provide hope
Drug companies big and small are now looking for alternatives to chemo.
One of the hottest new modalities is something called bispecific antibodies.
While antibody-based drugs have been around for several decades, bispecifics are modified antibodies that can identify two targets at once, thereby bringing T cells, which are a key component of our immune system, within reach of the targeted cancer cell.
The highest-profile bispecific cancer drug that’s been approved by the FDA is blinatumomab for a rare type of B-cell acute lymphoblastic leukemia.
There also are reportedly more than 200 other bispecifics either in clinical trials now or in the near future.
One of those is REGN1979, which achieved a 100 percent response rate and an 80 percent complete response rate in a trial of 10 patients with relapsed or refractory follicular non-Hodgkin’s lymphoma, the second most common non-Hodgkin’s lymphoma and the most common slow-growing lymphoma.
The phase I trial also demonstrated an “acceptable safety and tolerability profile with no observed dose-limiting toxicities,” according to trial researchers.
There were “no clinically significant neurotoxicities, including no seizures or encephalopathy.”
Dr. Israel Lowy, head of clinical and translational sciences and oncology at Regeneron, the company researching REGN1979, says that while a high response rate is frequently observed in the first-line treatment of follicular lymphoma, “it is remarkable to see a 100 percent response rate in heavily pretreated, relapsed, or refractory follicular lymphoma patients.”
Lowry says the company plans to initiate a phase II trial next year investigating REGN1979 in relapsed or refractory follicular non-Hodgkin’s lymphoma, and perhaps as a potential first-line treatment for this disease.
For four decades, the standard of care for follicular non-Hodgkin’s lymphoma was cytotoxic chemotherapy.
Follicular lymphoma currently remains incurable, but recently approved targeted and immunotherapeutic agents have extended remissions and overall survival rates for people with the disease.
The standard of care for this cancer changed when the FDA approved the anti-CD20 antibody rituximab (Rituxan) for relapsed and refractory follicular lymphoma in 1997 and for first-line treatment of follicular lymphoma in 2006.
Since then, more novel agents have emerged to treat follicular lymphoma.
“We’ve seen a paradigm shift in the past five years, with most new treatment regimens incorporating novel targeted or immunotherapeutic agents,” Dr. Nathan Fowler, an associate professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, said in a statement.
The new treatments have improved care for patients with follicular lymphoma.
“Several long-term follow-up studies of patients who have received current standard therapies have shown that, unlike patients 10 to 15 years ago, most patients today will not die of their disease,” Fowler said.
Better treatment options for MDS
At Onconova, a biotech company based in the Philadelphia area, researchers are looking at a new targeted treatment for people with myelodysplastic syndromes (MDS), a form of blood and bone cancer.
Early trials have shown that this drug works well and has fewer harsh side effects than the current chemotherapeutic standard of care.
MDS are a family of rare disorders in which the bone marrow fails to make enough healthy red blood cells, white blood cells, or platelets.
The condition can rapidly progress to more advanced disease and ultimately to acute myeloid leukemia in roughly 30 percent of cases.
There have been no advances in treatment for MDS in more than a decade. The current standard of care is a chemo regimen that’s not curative and can cause serious side effects.
Dr. Shyamala Navada, assistant professor at Mount Sinai Health System in New York, is the principal investigator of a clinical trial for people with a high risk for MDS that combines its therapy, rigosertib, with azacitidine, a chemotherapy that’s the standard of care for MDS.
“Rigosertib appears to be safe and well-tolerated across multiple clinical trials,” she told Healthline.
“It does not appear to cause significant myelosuppression, which is a common side effect of chemotherapy,” she said. “Patients with MDS are at increased risk of infection and bleeding due to low blood counts.”
This isn’t just an American phenomenon.
Cancer patients worldwide are becoming more aware of new treatment options.
The tide is shifting everywhere from Europe to Africa to China, where several types of cancer are on the rise and research and clinical trials of non-chemotherapeutic treatments for many types of cancer are booming.
In China, biopharmaceutical companies, such as BeiGene, JW Therapeutics, Salubris Biotherapeutics, Cellular Biomedicine Group (CBMG), CStone Pharma, Innovent Biologics, Hengrui Medicine, CARsgen Therapeutics, and Nanjing Legend Biotech Co., are making their mark with checkpoint inhibitors, CAR T-cell immunotherapies, monoclonal antibodies, and other non-chemo agents.
BeiGene, which has offices in both China and the United States, is seeing results in several clinical trials of its immunologic and targeted therapies for several types of cancer, from chronic lymphocytic leukemia and Hodgkin’s lymphoma to mantle cell lymphoma and non-small cell lung cancer.
Dr. William Novotny, a researcher at BeiGene, told Healthline that his company is committed to providing patients in China and beyond with new and better treatments for a broad selection of cancers.
“The vision of the company is to become the next Genentech in Beijing,” Novotny said. “We’re looking at becoming a global biotech company with a broad oncology profile. We’re off to a great start. It has been an amazing journey, and we are excited about the future.”
A personal motivation
Photo courtesy of Bret Coons
Bret Coons, associate director of communications at Pharmacyclics, says that during his years as senior media relations associate for Northwestern Memorial HealthCare in Chicago, he saw the negative effects of chemotherapy.
“I saw the need for better therapies. Those patients were put through so much,” he told Healthline. “It took a toll on me emotionally. There were patients that I never will forget.”
That’s what brought him to AbbVie in 2016.
“I knew there was a real patient commitment at AbbVie, and I saw the potential to work at a company that was placing a very strong importance on research and development,” said Coons, who went from AbbVie to Pharmacyclics in 2017.
After Coons arrived at Pharmacyclics, his father received a diagnosis of kidney failure. Doctors told him it was caused by the chemotherapy he had undergone for his testicular cancer.
“I’m happy he was able to get the treatment that he could for his cancer. Without it he would probably not be here,” Coons said. “But with that in mind, can there be something better?”
Coons will be donating a kidney to his father in March.
He now appreciates more than ever the importance of the need for newer, safer cancer treatments, and of patients being aware of all treatment options.
“I like that I can be an educator and help get the word out about these new treatments,” Coons said. “Hopefully I’ve reached individuals and informed their healthcare decisions.”