Use the best drug available first for patients with metastatic breast cancer

Results of the retrospective, multicentre epidemiological study show that ORR per line of therapy, across the whole study population, halved by 50% from the first to the third line (41.6% to 20.1% respectively), and disease control rates (DCR) also fell.

“The findings matched quite well with our expectations, however, patients have fewer lines of therapy than clinicians think they have,” remarked Dr Antonio Llombart Cussac, Specialist in Breast Cancer and Chief of Medical Oncology Hospital Arnau de Vilanova in Valencia, Spain. Dr Llombart Cussac contributed patients to the study.
Metastatic breast cancer still presents a substantial challenge with an annual mortality of around 7,000 women in Spain and an overall median survival of nearly three years post-diagnosis. CASCADE aimed to characterise the history and clinical management of metastatic breast cancer from a representative cohort of patients treated within the Spanish National Healthcare System. Clinical and socio-demographic characterisation, progression-free survival (PFS), overall survival and responses to the different treatment lines were investigated.

“Patients have fewer lines of therapy than clinicians think they have.” Dr Antonio Llombart Cussac, Specialist in Breast Cancer and Chief of Medical Oncology Hospital Arnau de Vilanova in Valencia, Spain.

Dr Llombart Cussac explained that there was a paucity of information around the treatment of patients in the real world compared to data from clinical trials. He added that clinical trial patients do not reflect the mix of patients seen in the everyday clinic. “In this study we wanted to find out what happens to patients who are less fit than those who participate in trials.”

Patients with metastatic breast cancer diagnosed from January 2007 until December 2008 were followed up for 5-7 years in the national, longitudinal study. Thirteen public hospitals covering around 9% of the Spanish population were chosen in an effort to cover a sample representative of the national healthcare system. Of these, 422 patients received treatment.

“Hospitals came from a range of big and small institutions, giving a picture of how these patients are being treated in Spain. We insisted that all patients treated during the defined time period were included, the good and bad scenarios,” said Dr Llombard Cussac.

The researchers recorded the type of treatment received (chemotherapy, hormone therapy, anti-HER2 therapy and other targeted therapies), the tumour type, patient characteristics, the PFS and the OS. “We wanted to know the median number of lines of therapy received, when a patient was diagnosed with metastatic breast cancer.”

In terms of histological tumour type, 29% were HER2 positive, 60% HER2 negative, and 16% were triple negative.

With each line of therapy added, there was a correlating gradual decline in both ORR and DCR regardless of treatment choice. Clear differences in response rates where seen among the HER2 negative subtypes, and triple negative tumours were the least responsive of all. Both tumours showed 40% ORR in the first line, while only HER2 negative/hormone receptor positive maintained an average 17% along disease progression.

“Triple negative cancer was the devil in this scenario because these patients did very badly,” Dr Llombart Cussac emphasised.

HER2 positive subtypes also saw treatment response differences throughout disease progression: both HER2 positive/hormone receptor negative and HER2 positive/hormone receptor positive showed declining ORR. Hormone therapy for HER2 positive/hormone receptor positive provided a more sustained response.

Median overall survival was around 26-27 months, as expected, and was the same whether patients responded to the first-line and the second-line therapies, responded only to the first-line therapy, or responded only to the second-line therapy. This translated into a statistically significant increase in overall survival of 15.2 months in these responders compared to those who did not respond to first- or second-line therapies across the whole study population.

Also, de novo metastatic breast cancer exhibited a significant OS advantage over recurrent disease and there was a statistically significant 22.2 months’ OS increase, on average, for first-line responders for both recurrent and de novo patients.

Three median lines of therapy

Dr Llombard Cussac expressed surprise at the number of lines of therapy a patient with metastatic breast cancer receives. “The surprise was that as clinicians we want these metastatic breast cancer patients to survive for longer and we aim to achieve four or five lines of treatment, but this study shows we are wrong,” he explained. “In fact, we found that the median number of lines that patients receive in the metastatic setting is around three. Many patients die before getting to three or four lines of therapy.”

He stressed that this highlighted the importance of administering the best available drug as soon as possible. “Don’t think your patient will achieve the third or fourth line and in doing so that you are optimising the drug, because a large number of patients will have passed away.”

“Patients that respond to the first line of therapy are those that respond also to the third and fourth lines,” said Dr Llombart Cussac. “There is a significant correlation between the first two lines of therapy and the behaviour of these patients. If you have a good drug, then use this first and not later.”

Based on De Paz Arias L, Garcia Teijido P et al. CASCADE study: pronounced decline in treatment efficacy through the metastatic life of breast cancer patients (248P). Presented on Monday 10 October 2016.

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