Tool predicts chemotherapy-related adverse effects among older adults with breast cancer

By: Jennifer Byrne

From: healio.com

Age has been identified as a risk factor for complications and toxicities related to various cancer treatments.

Additionally, many of these treatments may hasten the aging process in certain patients, according to Mina S. Sedrak, MD, MS, deputy director of clinical trials for the Center for Cancer and Aging Research at City of Hope.

“We’re beginning to understand that some of the cancer treatments that we give our patients accelerate the aging process, especially in older adults,” Sedrak said in an interview with Healio. “So, if we give them a treatment, we could cause them to age faster than their peers. This means they can develop more adverse health effects.”

These effects may include functional impairments that can limit the ability to perform everyday tasks and recreational activities.

According to a study published in The New England Journal of Medicine, more than 72% of older patients with cancer would not opt for cancer treatment that would result in functional impairment, even if it prolonged survival.

With that in mind, Sedrak and colleagues developed a tool — the Cancer and Aging Research Group-Breast Cancer (CABG_BC) Score — that estimates the likelihood of severe or life-threatening reactions to chemotherapy among older adults with early-stage breast cancer.

Sedrak spoke with Healio about the development of this risk-assessment tool, its capabilities, and the need to mitigate and manage treatment-related adverse events among older adults with cancer.

Question: How can premature aging due to cancer treatment affect older patients?

Answer: A growing body of literature suggests that cancer and its treatment can contribute to accelerated or premature aging. Treatments that spare cancer survivors from cancer-specific mortality can also shorten their healthy years of life. Older patients, in particular, more commonly develop adverse health effects, which can culminate in frailty and functional impairment, and at an earlier time than the general population. For example, a patient might develop neuropathy during chemotherapy, which may or may not improve. If it does not improve, then they could be left with disabilities such as more falls and inability to button a shirt or perform other everyday tasks. We may be extending their lives, but are we also shortening their healthy years of life? This continues to be the challenge in how we care for older adults with cancer as we try to balance the benefits of treatment with the concern for these age-related adverse consequences.

Q: Do these adverse effects sometimes prevent older patients from completing treatment?

A: Yes. That is certainly another problem we continue to face in the care of older adults with cancer. If an older patient develops severe toxicities from treatment, it might limit the delivery — or the effective delivery — of the planned cancer treatment. Often, this means a patient may start on chemotherapy but can’t finish the course because of the severe side effects and toxicities. They are left with all these adverse consequences, but none of the benefits.

Q: Could any of these adverse effects be reversed once treatment is stopped?

A: A lot of the effects could be managed by tertiary prevention. So, we manage complications of the neuropathy and symptoms like fatigue and pain, as well as other age-related issues like frailty, disability and multiple conditions. At the time of treatment or before treatment, we can strike a nice balance of optimizing their lives and giving them the best opportunity for survival while ensuring no detrimental effect on the quality of their survival. However, we currently don’t have any therapeutic interventions to prevent, slow or reverse these conditions. That’s another area we’re working on, and I think it’s an important area when we think about future cancer and aging research.

Q: What prompted you to develop this tool and how does it work?

A: Physicians who care for patients with cancer are no longer just focusing on curing the disease, but also on maintaining function. Especially in breast cancer, there are a lot of efforts centered on de-escalating therapy. All the studies in breast cancer have shown that patients may not need as much chemotherapy or hormonal therapy, or for as long a period.

So, considering this, we sought if there was an opportunity to personalize care for the patient. Precision medicine is all about new drugs that target tumors. As geriatric oncologists, we believe it is important to understand not only the tumor, but also the patient in whom the tumor resides. So, we’re asking what we can learn by comprehensively assessing patients prior to treatment to help us predict what will happen to them, so we can select the right drug for that patient and tumor.

We started by identifying a cohort of people aged 65 years or older who were scheduled to receive chemotherapy in the neoadjuvant or adjuvant setting for stage I, stage II or stage III breast cancer. We collected information from the medical charts, physicians and patients themselves, including the chemotherapy they were going to get, the planned dose, their baseline hemoglobin and liver function, their labs, and information about their functional status. These tools are part of a geriatric assessment developed by Arti Hurria, MD, who first conceptualized and led the current study. During treatment, we monitored patients and evaluated those who had grade 3 or higher adverse effects. We then looked at initial predictors at baseline for these effects. That’s how we created this predictive model, which is really a risk score based on these eight variables: use of an anthracycline chemotherapy, stage II or stage III breast cancer, planned treatment duration of more than 3 months, abnormal liver function, low hemoglobin, falls, limited walking ability and lack of social support. The scores can be calculated, and the total score can be used to create three risk categories: low, medium and high.

Q: How has this tool performed?

A: Once we developed the tool, we validated it in another cohort of women. In the validation cohort, we found that not only is it a good predictor, but when we compared it with Karnofsky performance status, our tool did significantly better. These measures tell us that we have a better way of identifying the possibility of adverse effects early on, prior to treatment.

Q: Will this have a role in clinical practice?

A: Yes. The goal is to make the tool as user-friendly as possible so that clinicians and other providers will be able to use it to facilitate conversations with patients about risks and benefit. I don’t think the tool by itself is going to be, or should be, the only factor that clinicians or patients consider when deciding treatment. However, I think this tool will provide a platform on which these conversations can be guided, along with clinical judgment and patient preferences. There are prehabilitation or habilitation interventions that we could give prior to or during chemotherapy to patients who are at high risk. These provide support to minimize adverse events, or to address them early before they become significant and cause a lot of problems. Studies that we and others have done have shown that supportive care interventions can be targeted for this population or intensified to reduce the side effects.

Q: Is there anything else you would like to mention?

A: Prediction is not necessarily the same as what happens. That’s why I think the message should be that this is part of the toolbox of things we can use to better personalize care.