WHILE CANCER TREATMENT helps rid the body of the disease, it brings with it the risk of toxicities that can negatively impact patients’ lives well after treatment ends.

“The side effects we cause last, and they can last a long time,” Don S. Dizon, a medical oncologist at Rhode Island Hospital in Providence, said during a Dec. 5 session at the San Antonio Breast Cancer Symposium (SABCS). “Our responsibilities to our patients do not end when cancer treatment ends, and we need to remember that.”

Dizon reminded attendees that treatment can impact people with cancer often in ways not typically captured by scientific studies, such as when a mother’s nausea prevents her from driving her child to school. “The amount of suffering and toxicities that people experience [is] vastly undercounted” by current toxicity criteria, he said, calling on oncologists to focus on patient-informed outcomes.

“We must learn from those we hope to treat and hope will live through a cancer experience,” he said.

Dizon’s comments on the importance of patient feedback followed presentations on five new studies focused on evaluating patient-informed outcomes among people with breast cancer to potentially reduce treatment toxicities and improve quality of life.

Kisqali Use in Elderly Patients

Some estimates say less than 25% of cancer clinical trial participants are age 70 or older, even though more than 40% of cancer patients belong to this age group. Because of this, trial results often aren’t clear on how elderly people with cancer may respond to newly approved drugs. With that in mind, a new analysis looked specifically at how elderly patients responded to a recently approved breast cancer drug.

In 2017, the Food and Drug Administration (FDA) initially approved the CDK4/6 inhibitor Kisqali (ribociclib) for use in women with hormone receptor (HR)-positive, HER2-negative advanced breast cancer in combination with hormonal therapy. Using data from the three original trials that led to Kisqali’s approval, the analysis looked at outcomes for 1,229 participants with HR-positive, HER2-negative advanced breast cancer split into three age groups: younger than 65, 65 to 74, and 75 or older. While some received Kisqali and hormonal therapy, others received a placebo and hormonal therapy.

Participants receiving Kisqali in all three age groups had similar overall and progression-free survival rates, time to chemotherapy, and scores on pain and fatigue questionnaires. “The benefit … was maintained in the older age group consistent with the other trials,” said Lowell Hart, a study author and an oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina.

While people younger than 65 had adverse effects similar to the overall population in Kisqali’s approval studies, those in the 65-to-74 and 75-plus groups who received Kisqali reported additional side effects, including low white blood cell levels, nausea, fatigue and diarrhea. Hart said this led many older participants to stop that treatment. However, a previous study showed doctors can lower a patient’s Kisqali dose to reduce the side effects while retaining the drug’s benefits. “There’s an opportunity to optimize adverse event management,” Hart said.

Quality of Life with Truqap Use

In November 2023, the FDA approved the AKT inhibitor Truqap (capivasertib) for use in adults with HR-positive, HER2-negative locally advanced or metastatic breast cancer with at least one genetic mutation, in combination with the hormonal therapy Faslodex (fulvestrant). The approval was based on results of a phase III trial presented at last year’s SABCS and published June 1, 2023, in the New England Journal of Medicine.

In a subsequent analysis of trial results, researchers looked at patients’ experiences while taking Truqap. The 708 participants—who were randomized to receive Faslodex plus either Truqap or a placebo—were asked to complete three questionnaires assessing drug tolerability, symptoms and function at various points during the trial.

Mafalda Oliveira, a study author and a medical oncologist at Vall d’Hebron University Hospital in Barcelona, Spain, reported researchers found no clinically meaningful differences between the two groups in participants’ responses about side effects. The one exception was diarrhea, with those taking Truqap reporting this side effect had a significant impact on their quality of life during treatment. While people in both groups ended the trial with similar quality-of-life scores, the time to decline was longer in those taking Truqap. “The results of this [patient-reported outcomes] analysis further support a positive benefit-risk profile for the combination of capivasertib [Truqap] and fulvestrant [Faslodex] in [aromatase inhibitor]-resistant, HR-positive, HER2-negative advanced breast cancer,” Oliveira said.

De-escalating Radiotherapy

De-escalation is a growing trend in cancer care, as oncologists figure out methods for exposing people to fewer or less-toxic therapies—avoiding more taxing side effects—while still treating the disease. However, researchers are still investigating the impact treatment de-escalation has on patients’ emotional responses. Could forgoing additional treatment make people more fearful their cancer could return? That was the question researchers asked in a recent analysis of an Australian de-escalation trial.

In the original study, published online Dec. 5, 2023, in the Lancet, researchers used MRIs and tumor pathology to assess the likelihood of cancer recurrence in 443 women who had undergone surgery for breast cancer. Based on those results, they were assigned to either receive radiotherapy, which is standard care, or go without radiotherapy. All participants received hormonal therapy. After five years, 1% of the women who omitted radiotherapy had a recurrence, compared with 1.7% of those who received radiotherapy.

The analysis presented at SABCS looked at quality of life and fear of cancer recurrence among these patients. “As expected … those who omitted radiotherapy had substantially improved quality of life compared to the others,” said Bruce Mann, a study author and a surgical oncologist at Royal Melbourne Hospital in Australia. Women who did not have radiotherapy reported less pain and better body image and physical function.

What wasn’t expected, however, was the impact on fear of cancer recurrence. Researchers had hypothesized that women who omitted radiotherapy would have more fear, thinking they had forgone an opportunity to prevent cancer. The result turned out to be the opposite, with 62% of women who had radiotherapy reporting a normal level of fear compared with 35% in the radiotherapy group. “There was a dramatically reduced amount of fear of cancer recurrence in those who omitted radiotherapy,” Mann said. Researchers theorized the women who received radiotherapy had higher fear because the results of their MRI and pathology indicated a higher risk for recurrence.

Mann noted the importance of identifying people who can have de-escalated treatment due to the associated improvements in quality of life and fear of recurrence.

Sleep Quality and Well-being

Another study looked at how a cancer diagnosis can impact a person’s sleep and, in turn, their well-being. Researchers administered sleep health and quality-of-life questionnaires to 1,409 women with newly diagnosed stage I to III breast cancer in Alberta, Canada, between 2012 and 2019.

Researchers found 56% of women reported insufficient sleep quality, and 41% reported sleeping for either less than six hours or nine-plus hours per night. Short sleep duration was associated with worse mental well-being, while poor sleep quality was associated with worse mental and physical well-being. The time when participants slept was not associated with a change in quality of life.

“This cohort study highlights the high prevalence of poor sleep health in women newly diagnosed with breast cancer, and these sleep issues negatively impact their quality of life,” said Lin Yang, a study author and a cancer epidemiology and prevention researcher with Alberta Health Services in Calgary.

Yang said further research should look at potential interventions to improve patients’ sleep quality.

Long-term Peripheral Neuropathy

Chemotherapy is a common treatment for people diagnosed with breast cancer, but it comes with the potential side effect of peripheral neuropathy, which is nerve damage that causes numbness and pain in the hands and feet. A recent French study investigated the duration of peripheral neuropathy and what characteristics put patients at highest risk for developing this debilitating side effect.

The study followed 11,014 people diagnosed with stage I to III breast cancer. Researchers found 29% experienced peripheral neuropathy six months after the end of treatment. The side effect persisted in many of those participants, with 27%, 20% and 13% experiencing peripheral neuropathy at one, three and five years after treatment, respectively. “There is a high burden of peripheral neuropathy [lasting] up to five years,” said Paul Cottu, a study author and a medical oncologist at Institut Curie in Paris.

Researchers looked at patients’ baseline characteristics to see if they could find a connection with risk for peripheral neuropathy. They found that having a previous neurological condition and exposure to taxane-based chemotherapy were associated with both early and long-term peripheral neuropathy. Additionally, people who developed peripheral neuropathy in the first six months following treatment have a high risk of experiencing the side effect for a long period of time, as nearly 50% of those patients still had peripheral neuropathy at the five-year mark.

Researchers noted the importance of assessing risk for peripheral neuropathy on an individual basis.

Thomas Celona is the associate editor for Cancer Today.