Breast Cancer Drug Dose Can Be Safely Lowered to Improve Side Effects

Decreasing Ribociclib Dose Doesn’t Lower Survival for HR+/HER2- Advanced Breast Cancer

More good news about breast cancer drug ribociclib (Kisqali) emerged from the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Reducing the ribociclib dose doesn’t affect the overall survival (OS) benefit in post-menopausal patients with hormone receptor-positive, human epidermal growth factor receptor2-negative (HR+/HER2-) advanced breast cancer.

Lowell L. Hart, MD, who is the scientific director of clinical research at Florida Cancer Specialists and Research Institute, shared the findings during a poster session at the meeting in Chicago on Monday, June 6, 2022 (Abstract 1017).

Dr. Hart drew data from the MONALEESA-2 trial, which evaluated the targeted drug ribociclib as a first-line treatment with letrozole (a type of drug known as an aromatase inhibitor) for this patient group. At each of the landmark times analyzed in the study, patients had a similar OS benefit regardless of whether they’d had a dose reduction. The strength of the dose, the timing of the dose reduction, or the number of reductions didn’t affect OS.

“We did look at the patients that had a lower dose intensity, a medium dose intensity, and a higher dose intensity,” Dr. Hart said during the session’s question-and-answer period. “And there were about 20% of patients who had two dose reductions … and it wasn’t any different if [they] had two dose reductions.”

Dose reductions have become an increasingly critical topic in cancer care, and for good reason. When the doses of certain therapies are reduced, their side effects are reduced, too – even while some remain just as effective in treating cancer. With some drugs, lower dose, fewer side effects, and equal efficacy can occur simultaneously.

Ribocliclib’s Effect on Overall Survival for HR+/HER2- Advanced Breast Cancer

Ribociclib has shown great promise. When combined with fulvestrant (a type of drug known as a Selective estrogen receptor degrader), postmenopausal women with HR+/HER2- breast cancer experienced OS rates that were 16 months longer than patients who were only on fulvestrant. When combined with letrozole, median OS rates were more than a year longer compared to rates for letrozole alone for patients with HR-positive, HER2-negative advanced breast cancer.

Ribociclib can cause side effects in patients, however, including nausea, diarrhea, fatigue, or an increase in liver enzymes. Dr. Hart reported that during MONALEESA-2, about two-thirds of patients required a dose reduction, mostly due to adverse effects. Dr. Hart’s research offers oncologists and patients confidence and reassurance that such a decrease in dose will not adversely affect OS

The Importance of Dose Reductions

During the early days of chemotherapy, many doctors assumed that higher toxicity correlated with higher efficacy. Studies like Dr. Hart’s show otherwise. They show the potential that lowering the dose of certain drugs may reduce side effects while not affecting OS with the drug.

“Dose reductions can cause anxiety both for the patient and the oncologist,” says Dr. Aditya Bardia, director of breast cancer research and associate professor at Harvard Medical School in Boston, and an advisor to Dr. Hart’s study. “That's why analyses like these are important. They can assure the oncologist and the patient that if a dose reduction is needed for this drug, it will not compromise survival.”

Project Optimus, led by the U.S. Food & Drug Administration, is part of the effort to determine dosing that is optimal for efficacy, safety, and tolerability. The goal of cancer medication is to increase survival while maintaining quality of life, and dose reduction can play an important role in achieving that balance. Yet the effect of dose reductions varies by drug. Continuing research on dose reductions will allow doctors and patients to understand the potential risks and benefits of a dose reduction when making medical decisions.

“Every drug is different, so it’s important to have analyses like these, which provide additional confidence that reducing the dose not only will maintain the quality of life, but will not have any deleterious effects on survival,” Dr. Bardia says.

If dose reductions don’t affect OS benefits, one session participant asked, should the initial dose be lowered? Dr. Hart responded that clinical trials are currently examining this issue. But considering that the ribociclib dose can also be increased during treatment, he said that there may be times now when doctors choose to start patients on a lower dose.

Advice for Patients

Anne Loeser, the founder of the Patient Centered Dosing Initiative and a patient with metastatic breast cancer, says that many patients believe that they have a choice between quality of life versus quantity of life. Sometimes, she says, it’s not an either/or decision.

“Be very frank with your doctor about how you’re feeling on your drug. There may be options available to you, including dose reduction,” Loeser says. “Don’t always feel like you have to choose between either quality of life or quantity of life. In some cases, it might be both.”

Dr. Bardia echoed this point, stressing that the best way to determine optimal dosing is to start with open conversations between patient and oncologist.

“Patients should bring up their side effects to their doctor sooner rather than later,” Dr. Bardia says. “A lot of times, oncologists are not aware of a lot of the side effects for various reasons. Perhaps the patient doesn’t want to bother the oncologist or the patient is worried that it might mean a reduction in the dose or a treatment discontinuation that could impact her or his survival. But it’s important to have an open dialogue. The field is moving toward finding the right treatment and the right dose for each patient, rather than one size fits all.”