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Insights from the European Cancer Congress 2015 (Vienna, 25-29 Sept.): Dr. Fatima Cardoso on Advanced Breast Cancer

Intro text: 

 

During the European Cancer Congress, which took place in Vienna from 25 to 29 September 2015, findings of latest scientific research were discussed. It was announced that researchers have taken an important step towards understanding why primary breast cancers return while others do not. They have found that the genetic factors driving the cancers that recur are different from those found in the cancers that do not.

This discovery could enable doctors to identify patients at high risk of a recurring cancer. Furthermore, it could also enable doctors to target the genes responsible for recurrence when the cancer is first diagnosed, aiming at preventing the cancer’s return.

If individual cancers can change genetically over time, that would mean that treatments targeting a particular genetic mutation may have to change as the disease progresses. Rather than basing the treatment only on samples taken when the cancer is first diagnosed, the treatment can be continued, refined or adapted based on the results of regular samples of cancer tissue.

The aim of the DETECT Study Program, and of similar studies, is to evaluate whether treatment efficacy in women with metastatic breast cancer is increased by taking into account the molecular characteristics of Circulating Tumour Cells (CTCs).

Dr. Fatima Cardoso, Director of the Breast Unit of the Champalimaud Clinical Center in Lisbon, Portugal, and Chair of the EORTC Breast Cancer Group (member of BIG), attended the ECC 2015 and had the privilege of being a discussant during the session on Advanced Breast Cancer. She shares her insights on this topic.

Fatima Cardoso (FC): "The technique of Circulating Tumour Cells (CTCs) remains a very interesting one, with an important prognostic value. However, this logistically complex technique is unlikely to change clinical practice in the future. At present, we do not have sufficient data to use CTC as a predictive marker. To achieve clinical utility of CTC in (advanced) breast cancer, we would need more trials in which therapy decision making is based on CTC results. Some of these trials are ongoing such as the EORTC-BIG TREAT CTC trial. There are other techniques, such as the extraction from circulating DNA and RNA, which are also promising and may be logistically less challenging."

"The term ‘precision medicine’ is very fashionable. The definition varies from one scientist to another."

To the question "In what way will these findings have important implications for personalised medicine/precision medicine?", Dr. Cardoso replied: "The term ‘precision medicine’ is very fashionable. The definition varies from one scientist to another. In practice, you try to individualise as much as possible so that each patient receives a personalised treatment. In reality, however, we are still far from 100% individualisation. At present, we divide breast cancer in different subtypes, enabling us to apply different personalised treatments for each group of patients of the same cancer subtype. Furthermore, personalised treatment is not just based on biology. Not only do we have to tailor breast cancer treatment based on the type/subtype of the disease, we must also look at individual characteristics of each patient (such as clinical data, socio-economic factors, biological age, and most importantly patient preferences). In other words, there is still a lot to learn before we can really talk about personalised medicine or precision medicine."

The GeparQuinto study (Untch et al, 2012), a phase 3 trial, suggests that the addition of lapatinib to trastuzumab in combination with neoadjuvant chemotherapy significantly improves pCR rates in patients with HER2-positive breast cancer. In the neoadjuvant treatment of HER2-positive breast cancer patients, anthracycline- and taxane-based standard chemotherapy with concurrent (only with taxane) trastuzumab has shown to be more efficacious and less toxic than the standard chemotherapy with lapatinib.

FC: "The results of the primary endpoint of the trial had already been presented and showed higher pCR rates. During the ECC, the long-term outcome was presented. Despite higher pCR rates with treatment with trastuzumab than with lapatinib, there seems to be no difference in long-term outcome. After surgery, all patients received the same standard treatment of 1 year of trastuzumab, which may have contributed to the finding of a similar overall survival. Results of the study, combined with the findings of the NeoALTTO trial, confirms that trastuzumab is superior to lapatinib in the neoadjuvant setting, and that high pCR rates do not translate into better long-term outcome, calling for caution on decisions based solely on pCR rates."

Advances in understanding tumour biology, particularly signalling pathways, have led to the development and approval of many novel agents and have changed the landscape of therapy for patients with metastatic breast cancer.

At the ECC, updated data were presented from a phase 2 trial evaluating the use of enzalutamide as a single agent for the treatment of advanced triple-negative breast cancer (TNBC). Findings from the provisional analysis demonstrate the potential for a diagnostic test to help select women within this particularly aggressive type of breast cancer who may benefit from enzalutamide treatment.

The data presented at the ECC highlights the potential advantages of using a novel genomic profiling assay to identify patients who might respond to treatment.

"We are now able to individualise treatments based on the different subtypes of breast cancer."

FC: "As mentioned previously, we are now able to individualise treatments based on the different subtypes of breast cancer. TNBC is a heterogeneous breast cancer group, and identification of its subtypes is essential for understanding the biological characteristics and clinical behaviours of TNBC as well as for developing personalised treatments. One of TNBC’s subtypes is the Luminal AR, which is characterised by overexpression of the androgen receptor (AR). Researchers have developed an AR gene signature, called PREDICT AR, which shows the activation of the pathway/receptor, and seems to be linked to the responsiveness to enzalutamide. The phase 2 trial showed some clinical activity of enzalutamide in the PREDICT AR+ group. These finding as well as the true value of this biomarker must be confirmed in a phase 3 trial, which is already being developed."

During the ECC, results of the PEGGY trial were presented (a phase 2 randomised study of the PI3-kinase (PI3K) inhibitor pictilisib (GDC-0941) plus paclitaxel in patients with hormone receptor (HR)-positive, HER2-negative locally recurrent or metastatic breast cancer (mBC)). The conclusion: PEGGY did not meet its primary endpoint in either the ITT (Intent-to-Treat) or PIK3CA-mutant populations and revealed no significant benefit from adding pictilisib to paclitaxel for patients with HR-positive, HER2-negative locally recurrent or mBC.

FC: "The negative results open a lot of questions regarding the clinical application of these agents, particularly in view of their toxicity. Until now, unfortunately, Pi3K mutations have not been a reliable biomarker to identify patients who could benefit from this class of agents. The study also shows that there is a clear need for better understanding of biomarkers."

To conclude, Dr. Cardoso focused on the importance of quality of life of patients with advanced breast cancer and highlighted the following topic discussed at the ECC: “The Paloma-3 study, presented by Prof. Dr. Nadia Harbeck (Head of the Breast Centre of the University of Munich, Germany), showed that global quality of life was maintained on treatment at significantly higher levels with palbociclib plus fulvestrant, along with a significant improvement in emotional functioning and pain compared to placebo plus fulvestrant. This is clearly an important finding in the development of this agent. In an incurable setting such as advanced breast cancer, issues of quality of life and safety profile are of utmost importance."

"Governments to prioritise which medication should be available to everyone."

FC: "Nowadays, many of our discussions are focused on accessibility, availability and affordability of drugs. Unfortunately, new advances are not reaching all cancer patients equally. For example, many patients worldwide do not receive adequate pain relief. The continuous increase of the cost of new agents puts a huge burden in all health systems. In that sense, the ESMO Magnitude of Clinical Benefit Scale is an extremely useful tool to provide an objective way of assessing the true clinical benefit and impact of a new treatment; it may help governments to prioritise which medication should be available to everyone."