Soft chemotherapy is very effective in older patients when added to targeted treatment in aggressive breast cancer

February 10, 2018, European Organisation for Research and Treatment of Cancer

Avoidance of side-effects of chemotherapy is particularly important in the elderly, but finding the balance between reduced toxicity and maximum effectiveness is not always easy. A trial carried out by the European Organisation for Research and Treatment of Cancer, published today in The Lancet Oncology, shows that, in older patients with HER2 positive metastatic breast cancer (an aggressive breast cancer subtype where the cancer has spread to other parts of the body), a combination of a 'soft' chemotherapy with antiHER2 therapy is highly active and has low toxicity, important in a frail population.

Professor Hans Wildiers, a medical oncologist from the University Hospital Leuven, Belgium, and colleagues from Italy, the UK, Portugal, and France, randomised 80 to the targeted therapies trastumuzab and pertuzumab (TP) or to TP plus metronomic oral cyclophosphamide (TPM). The patients were aged 70 plus, or, if they were non-fit in other respects than their , 60 plus. The median age of participants was 76.7 years.

"We know that the chemotherapy agent docetaxel combined with TP is effective in younger patients with HER2 positive , but docetaxel is 'classical' chemotherapy that can be significantly toxic and thus affect quality of life (QoL) especially in older women. Of course, QoL is important for all patients, but it has special significance in the elderly, particularly when used for palliation," Prof Wilders says.

"We therefore decided to study whether combining TP with the 'softer' chemotherapy metronomic oral cyclophosphamide, would be active and have less toxicity than when used with docetaxel, or whether we could even omit chemotherapy and only administer TP in this age group. If tumour progression occurred after TPM or TP, patients would be eligible to receive another targeted drug, T-DM1, which is also generally well tolerated."

The researchers found that the TPM regime gave seven months longer progression free survival—the length of time during which a patient lives with the disease without it getting worse—compared with TP alone (median progression free survival 13 months versus six months). T-DM1 was also active, with a median disease control period of six months, after TPM or TP. Toxicity for all regimens was very acceptable in this frail population, they say. Nine out of the 29 deaths during the study period were not breast cancer-related.

"These results were encouraging," says Prof Wildiers, "since we found that, with gentle therapy, we could delay tumour growth in a significant proportion of for long periods. Our study also indicates that TPM and T-DM1 allow us to delay, or even avoid entirely, more toxic chemotherapy like docetaxel in these patients. In this age group, maintenance of QoL and the avoidance of toxic side-effects may be just as important as survival.

"We believe that there is a strong case for carrying out trials designed specifically for older people. However, financial support for such trials is very difficult to find. Additionally, older patients are far less likely to receive standard , and are also unlikely to be included in a randomised trial where there is a risk that they will receive a treatment with high toxicity."

Pharmaceutical companies are reluctant to support trials involving the elderly for a number of reasons, the researchers say. There is little direct benefit for companies, and unexpected toxicity may present new molecules in a bad light. Additionally, it is important to include frailty measurement in future trials; most trials include some elderly but only those who are fit. New drugs should also be evaluated in frail older persons, who represent a large proportion of the real-life population, they say.

Dr. Denis Lacombe, EORTC Director General, said: "These impressive results underline how important it is to investigate drug efficacy and tolerance in . Older people, particularly those who are frail, are a special case in exactly the same way as children are. We cannot and must not assume that because a drug is effective and relatively free of side effects in young to middle-aged adults that it will be the same for the elderly.

"Given that cancer tends to be a disease of old age, it is irresponsible to overlook special needs in this field. We hope that regulators will listen to our views and put in place measures designed to encourage industry to carry out that include the older and frail patients who make up a large proportion of those affected by cancer. Only this way will they get medicines that are not just effective against tumours, but that also meet the requirement of providing a good quality of life."

Explore further: EORTC study opens for elderly patients with HER-2 positive metastatic breast cancer

More information: Hans Wildiers et al. Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer (EORTC 75111-10114): an open-label, randomised, phase 2 trial from the Elderly Task Force/Breast Cancer Group, The Lancet Oncology (2018). DOI: 10.1016/S1470-2045(18)30083-4

Related Stories

EORTC study opens for elderly patients with HER-2 positive metastatic breast cancer

June 19, 2013
Despite the fact that the incidence of cancer is many fold higher in persons over 65 years of age, we still have an inadequate understanding on how best to treat these older cancer patients. Furthermore, even though elderly ...

T-DM1 improved overall survival for heavily pretreated patients with HER2-pos breast cancer

December 11, 2015
Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was ...

Adjuvant Trastuzumab did not improve outcomes for patients with HER2-low breast cancer

December 6, 2017
Adding trastuzumab (Herceptin) to standard adjuvant chemotherapy did not improve invasive disease–free survival for patients with early-stage breast cancer found to have low levels of HER2, as defined as immunohistochemistry ...

Ramucirumab plus docetaxel improves progression-free survival in urothelial cancer

September 11, 2017
Ramucirumab plus docetaxel improves progression-free survival in patients with advanced or metastatic urothelial cancer who have progressed on platinum-based chemotherapy, according to late-breaking results from the phase ...

Mature results favor pembrolizumab as second-line treatment for bladder cancer

September 11, 2017
Mature results from the KEYNOTE-045 trial to be presented today at the ESMO 2017 Congress in Madrid (1) have confirmed significantly longer survival in patients with advanced urothelial cancer who receive the checkpoint inhibitor ...

Capecitabine monotherapy does not improve survival in elderly patients with early-stage breast cancer

December 12, 2014
In elderly breast cancer patients with moderate- to high-risk early-stage disease for whom standard chemotherapy is too toxic, the chemotherapy capecitabine, which causes fewer side effects than the standard chemotherapy ...

Recommended for you

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 ...

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 ...

NEJM reports positive results for larotrectinib against TRK-fusion cancer

February 22, 2018
In 2013, the labs of University of Colorado Cancer Center investigator Robert C. Doebele, MD, PhD, and Dana-Farber Cancer Institute investigator Pasi A. Jänne, MD, PhD reported in Nature Medicine the presence of TRK gene ...

New therapeutic gel shows promise against cancerous tumors

February 21, 2018
Scientists at the UNC School of Medicine and NC State have created an injectable gel-like scaffold that can hold combination chemo-immunotherapeutic drugs and deliver them locally to tumors in a sequential manner. The results ...

Five novel genetic changes linked to pancreatic cancer risk

February 21, 2018
In what is believed to be the largest pancreatic cancer genome-wide association study to date, researchers at the Johns Hopkins Kimmel Cancer Center and the National Cancer Institute, and collaborators from over 80 other ...

Similarities found in cancer initiation in kidney, liver, stomach, pancreas

February 21, 2018
Recent research at Washington University School of Medicine in St. Louis demonstrated that mature cells in the stomach sometimes revert back to behaving like rapidly dividing stem cells. Now, the researchers have found that ...

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.