New drugs, however heralded, take time to embed into clinical care.
Enhertu, the powerful antibody-drug conjugate from Daiichi Sankyo and AstraZeneca, was first approved in the U.S. in 2019, before the world had even heard of a novel coronavirus. This past weekend, results presented at the American Society of Clinical Oncology’s annual meeting showed its potential for use in the first-line treatment of metastatic breast cancer, the result of steady work by its makers to test it in earlier and more widely.
Immunotherapies like Opdivo, Tecentriq and Imfinzi were first approved eight to 10 years ago. Now, after marching up through metastatic treatment of various tumors, data at ASCO demonstrated how they can be used more widely both before and after surgery in early cancer.
And bispecific antibodies, a relatively recent addition to physicians’ treatment tool kit, are slowly being absorbed into practice, with some tinkering to manage their side effects. Likely a few of the experimental drugs featured over the past few days at ASCO, such as camizestrant or vepdegestrant, will go on to win approval in the years ahead.
Gauging which of these data are truly “practice-changing” is best left for future meetings, but the BioPharma Dive team nonetheless has a few reflections after attending this year’s. Read on for three of our takeaways:
Positive breast cancer data comes with caveats
This year, ASCO was headlined by promising clinical trial results for several new breast cancer drugs.
Enhertu could change the frontline standard of care for an aggressive kind of metastatic breast cancer. Vepdegestrant, an experimental targeted medicine, may help control tumor growth in a common type. And camizestrant, also from AstraZeneca, proved effective at sustaining the benefit patients with that more common tumor experience on first-line therapy.
“Across the board, we have practice changing data that were presented for every sub-type of breast cancer, which is really exciting” said Nancy Chan, a medical oncologist specializing in breast cancer at the NYU Langone Perlmutter Cancer Center.
There are important qualifications to the good news, however. Enhertu showed strong benefit as part of first-line treatment for metastatic tumors that are positive for a protein called HER2. But it comes with a dangerous side effect that may make doctors cautious about adoption if it’s approved in this setting. Moving Enhertu earlier also raises questions about what to use afterwards, since the ADC plays an important role in second-line treatment currently.
Vepdegestant, a pill, has promise treating breast cancer patients whose tumors are estrogen receptor positive but lack the HER2 protein. Its efficacy over the common therapy fulvestrant was limited to only patients with mutations in a gene called ESR1, though; those patients without one didn’t appear to benefit.
A physician interviewed by Cantor Fitzgerald analyst Li Watsek’s team was disappointed the drug “didn’t show greater differentiation,” Watsek wrote in a Monday note to clients.
Adding camizestrant into clinical practice, meanwhile, will require greater adoption of a blood test used to monitor for those ESR1 mutations, which doctors fear may be costly and arduous.
Still, the data presented should give doctors more options for controlling advanced breast cancer. And they may offer advantages important to patients, too. “It’s not a small change to remove the intramuscular injection of fulvestrant and change to oral,” said Chan, about the vepdegestrant data. “That gives the patient back so much more control and significantly improves their quality of life.” — Ned Pagliarulo, Delilah Alvarado
Bispecific drugs need troubleshooting
In just a few years, bispecific antibodies have gone from exciting innovation to a common part of clinical practice, used to treat not only late-stage blood cancers but also earlier-stage disease in some tumors. A whole cohort of new ones are in testing, making the field an active area of pharma dealmaking.
But they carry immune-related side effects that were previously only seen with complex CAR-T cell therapies. Physicians must now also weigh those risks for a broader group of patients than before. Because they’re meant to be given as outpatient treatment — CAR-Ts are often administered in a hospital — some oncologists are cautious about using them, fearing patients may not be able to receive hospital care before the side effects they might experience cause serious illness or death.
The specific conditions are known as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both aggressive responses resulting from the activation of immune cells. In the case of Amgen’s newly launched lung cancer drug Imdelltra, a little more than half of study participants had CRS, usually after the first two doses. Around one in seven had ICANS, usually within the first 30 days, Abdul Rafeh Naqash, immuno-oncology director at the University of Oklahoma’s Stephenson Cancer Center, said in a panel discussion at ASCO, citing data from a pivotal trial.
Melissa Johnson, director of lung cancer research at Sarah Cannon Research Institute, argues Imdelltra can be used outpatient by giving patients monitoring tools like thermometers, blood pressure cuffs and blood-oxygen monitors to detect side effects. The steroid dexamethasone could also be used to tamp down immune response. To reduce hospital stays with CAR-T patients, Sarah Cannon has tested wearable devices that provide continuous monitoring, Johnson said, which could be used for patients on bispecifics, too.
“There are more bispecifics coming in solid tumor oncology,” she said. “So we have to grapple with these things now so that we’ll be able to give bispecifics for our prostate cancer patients and our breast cancer patients, where the CRS events may be more significant.” — Jonathan Gardner
U.S. science cuts feed undercurrent of alarm
ASCO’s hundreds of sessions were, by and large, concerned with the ins and outs of cancer study data and clinical practice. In that respect, this year’s meeting was much the same as it always is.
But the Trump administration’s aggressive downsizing of the federal health workforce and planned curtailment of science spending rippled through the meeting nonetheless.
The White House’s budget calls for major reductions in funding for the National Institutes of Health and National Cancer Institute, which could imperil future cancer drug research. ASCO CEO Clifford Hudis used the meeting’s opening session to warn of the cuts’ likely impact.
“We find ourselves in a tragic paradox,” he said on Friday. “We are living in a time of unprecedented scientific opportunity, yet we are facing historic reductions in the very resources we need to turn these opportunities into hope for millions of patients counting on us.”
Chan, at the Perlmutter Cancer Center, told BioPharma Dive the effects are already becoming apparent. “Across the board, we definitely are seeing a decrease in oncology funding for new ideas and new concepts, both at the clinical level and also at the translational basic sciences level,” said Chan. “I think that will have a long-term impact.”
Research that primarily looks at cancers affecting women, and related issues they may experience, could be most at stake. Trump has issued executive orders that target gendered language and DEI programs, potentially raising barriers for researchers seeking federal grant funding to study women’s health.
“Regardless of where you are from in the world, breast cancer is the most common diagnosis in women for most countries,” Chan said. “This is a common issue for all of us.”
About one in 12 women will be diagnosed with breast cancer in highly developed countries. It is one of the most studied cancers in the U.S., and data from studies of new treatments were featured across this year’s meeting. — Delilah Alvarado
