Older women with HR-positive breast cancer may receive similar benefit from CDK 4/6 inhibitors as younger women

December 8, 2017, American Association for Cancer Research

Older women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer who were treated with cyclin-dependent kinase inhibitors 4 and 6 (CDK4/6) achieved progression-free survival at a rate similar to that of younger women, according to data presented at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5–9.

In the past two years, the U.S. Food and Drug Administration (FDA) has approved three CDK4/6 inhibitors: palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio). The drugs work by blocking the function of proteins CDK4 and CDK6, both of which drive cell multiplication, fueling tumor growth. Previous research has shown that for patients with HR-positive metastatic breast cancer, combining a CDK4/6 inhibitor with endocrine therapy improves progression-free survival (PFS) compared to endocrine therapy alone.

"As we approve new drugs to treat cancer, it is important to try to improve our understanding of the efficacy and safety of these drugs in our older patients," said the study's lead author, Harpreet Singh, MD, scientific liaison for Cancer in Older Adults and a medical officer in the Office of Hematology and Oncology Products, Center for Drug Evaluation and Research at the FDA. "Older patients traditionally have been underrepresented in oncology , so pooling outcomes of older patients across clinical trials in the same drug class allows us to gain insight into how these patients may benefit."

In this study, Singh and colleagues pooled and analyzed data from prospective, randomized studies of three different CDK4/6 inhibitors in combination with an aromatase inhibitor for the initial treatment of postmenopausal patients with HR-positive . Using Kaplan-Meier estimates and a Cox-proportional hazard model, they explored the effect of age on progression-free survival.

Of 1,334 total patients, 42 percent were 65 or older, and 24 percent were 70 or older. For patients 70 or older who were treated with a CDK4/6 inhibitor in combination with an aromatase inhibitor, the estimated PFS was not reached, compared with an estimated PFS of 18 months for those treated only with an aromatase inhibitor.

For patients under 70 treated with a CDK4/6 inhibitor, the estimated PFS was 23.5 months, compared with an estimated 13.8 months for those treated only with an .

The researchers also evaluated safety in the patients who had taken at least one dose of CDK4/6 inhibitor. The study showed that the older patients were more likely than the younger patients to discontinue treatment due to side effects: 20 percent of the patients 70 or older discontinued treatment, compared with 17 percent of the patients 65 or older and 8 percent of the patients under age 65. Singh said the most common events that led to discontinuation of treatment across all age groups were infection, fatigue, blood count abnormalities (neutropenia), liver enzyme abnormalities, and diarrhea.

"Our findings suggest that there is no treatment difference across age subgroups in terms of efficacy of CDK4/6 inhibitors," Singh said. "This is an important piece of information as and patients weigh their treatment options as new therapies are approved."

Coauthor Lynn Howie, MD, a medical officer in the same division of the FDA, added that the potential benefit for older breast cancer patients should be weighed against risk of toxicity. In addition to the higher rates of discontinuation of treatment, older patients often required more modification of dosages to help them manage side effects.

"Health care providers should counsel each patient individually on the potential benefit of these therapies as well as the potential risks, taking into account the patient's disease characteristics, performance status, comorbidities, social support, and treatment preferences," Howie said.

The authors added that as the population ages, the FDA and other stakeholders are exploring ways to increase the representation of older in clinical trials to gain more information on how to treat with cancer.

The study's primary limitation is the relatively small numbers of enrolled in the clinical trials, particularly those over 75. Singh noted that many older adults who enroll in clinical trials are healthier than their peers, with fewer comorbidities and less frailty, so their results may not be representative of the broader population.

Explore further: New breast cancer drug may benefit younger women, too

Related Stories

New breast cancer drug may benefit younger women, too

December 6, 2017
(HealthDay)—Adding a new drug to standard treatment can slow the progression of advanced breast cancer in younger women, a new clinical trial has found.

Abemaciclib initial therapy improves outcome in endocrine-sensitive advanced breast cancer

September 11, 2017
The results of the MONARCH 3 trial, presented at the ESMO 2017 Congress in Madrid, showed that adding the cyclin-dependent kinase (CDK) 4/6 inhibitor abemaciclib to endocrine therapy improved progression-free survival compared ...

Adding everolimus to fulvestrant improved outcomes for postmenopausal patients with HR-positive breast cancer

December 8, 2016
Progression-free survival was more than doubled for patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer resistant to aromatase inhibitor therapy by adding everolimus (Afinitor) to treatment ...

Study shows biomarkers can predict which ER-positive breast cancer patients respond best to first-line therapy

June 27, 2017
Two challenges in treating patients with estrogen-positive breast cancer (ER+) have been an inability to predict who will respond to standard therapies and adverse events leading to therapy discontinuation. A study at The ...

Targeting estrogen receptor improves progression-free survival in advanced breast cancer

October 8, 2016
Fulvestrant significantly increases progression-free survival in women with hormone-receptor-positive advanced breast cancer, particularly those with less aggressive lower-volume disease, researchers reported at the ESMO ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.