SABCS 2018: Highlights in breast cancer treatment

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Published: 13 Dec 2018
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Dr Matteo Lambertini - San Martino Hospital, Genoa, Italy

Dr Matteo Lambertini provides a roundup of what was being discussed in breast cancer at the SABCS 2018 congress in San Antonio with a focus on patients. 

Dr Lambertini begins by explaining the importance of the results of the KATHERINE study into patients with HER2-positive breast cancer where the use of T-DM1 antibody drug, instead of standard therapy, was shown to significantly improve outcomes for patients.

He also reports on a study on early stage breast cancer from the EBCTCG that pooled results of 11 trials adjuvant endocrine therapy after 5 years of endocrine therapy, with it being seen that extended endocrine treatment is a positive,

Dr Lambertini shares a study on triple negative breast cancer where there was found to be no benefit of extending treatment after chemotherapy to the additional agent capecitabine.

Here at the San Antonio Breast Cancer Symposium 2018 we had presentations of many important studies that will have a major impact on the way we treat our breast cancer patients but I wanted to discuss mainly three studies in the setting of early stage breast cancer. These important studies that have a direct impact on the clinical management of these patients are the first one for women with HER2 positive disease, the second for patients with hormone receptor positive breast cancer, and finally for women with triple negative disease.

In the HER2 positive setting the most important trial is the KATHERINE study that has just been published in The New England Journal of Medicine concurrently with the oral presentation. This is a randomised study in approximately 1,500 patients with HER2 positive breast cancer that received neoadjuvant chemotherapy, taxane-based chemotherapy, with trastuzumab-based treatment and did not achieve a pathologic complete response so that had residual disease at the time of surgery. After surgery patients were randomised to continue trastuzumab as per standard of care or to move to TDM1, so another anti-HER2 agent. The use of this treatment significantly improved the outcomes of these patients in terms of more than 11% absolute gain in disease free survival at three years, almost 50% reduced chance of disease relapse with the use of TDM1, and this is very solid data. Also considering the fact that this patient population received what is the current standard of care, so taxane-based chemotherapy, in 75% of patients also anthracyclines, so anthracycline taxane-based chemotherapy and also 20% of these patients received dual anti-HER2 therapy in the neoadjuvant setting, so trastuzumab plus pertuzumab. In all the patient subgroups, including among patients that received dual anti-HER2 therapy in the neoadjuvant setting, the use of TDM1 in this patient population appears to be particularly important, associated with a great benefit.

We have to acknowledge the fact that we had 18% of patients that discontinued TDM1 because of toxicity, so this is very important to manage in everyday clinical practice. The most important side effects were thrombocytopenia, liver toxicity, nausea, were the most important side effects. So, based on these results the way we treat early stage HER2 positive breast cancer will change in the next days. The main message is that patients with stage 1 HER2 positive breast cancer are nowadays candidates to receive surgery first and then the Dana Farber regimen with weekly paclitaxel and trastuzumab; these patients are doing very well with only taxane single agent and trastuzumab for a year. For patients with stage 2 and stage 3 breast cancer, HER2 positive breast cancer, nowadays we have to treat mainly these patients in the neoadjuvant setting with taxane or anthra-taxane chemotherapy with trastuzumab and, if available, also pertuzumab. Then if patients achieve a pCR they can continue the same anti-HER2 treatment for a year but for patients without a pathological complete response in this case it’s of benefit to switch to another HER2 therapy which is TDM1.

Moving now to the early stage breast cancer, hormone receptor positive disease, the most important study is the individual patient level meta-analysis by the Early Breast Cancer Triallists Cooperative Group. What these authors have done was to include data from eleven trials, more than 22,000 patients, that received extended adjuvant endocrine therapy with aromatase inhibitors after five years of endocrine therapy. What the authors did was to pool the results from all these studies that assessed the efficacy of more than five years of endocrine therapy, they analysed three main groups of patients – patients who received five years of aromatase inhibitors after five years of tamoxifen; the second group those who received five years of aromatase inhibitors after prior 5-10 years of tamoxifen and aromatase inhibitors and finally the group of patients who received five years of aromatase inhibitors after prior five years of aromatase inhibitors. The two main messages from this large analysis – the benefit of using aromatase inhibitors for five additional years, so extended therapy with aromatase inhibitor, is mostly observed for patients that received prior tamoxifen, in this case approximately 3.6% absolute benefit in relapse free survival, more than 30% reduced risk of developing disease relapse, but the benefit became very small, slightly more than 1% absolute benefit in disease free survival at five years in the population of patients that received aromatase inhibitors in the first five years. The second important message is that the benefit was mostly observed for patients with node positive disease, so high risk patients, again from 1% benefit in node negative patients up to more than 7% absolute benefit for patients with more than four positive nodes. So these are the two most important considerations to be discussed with our patients when we have to counsel them about the possibility to extend treatment up to ten years or beyond the first five years of adjuvant endocrine therapy.

These are not actually the final results of this meta-analysis, we are going to hear more about that in the future because after this presentation we had the presentation of a trial from our Japanese colleagues on the same topic, a study in which the authors assessed the efficacy of five years of aromatase inhibitors after prior five years of aromatase inhibitors. So these results will be matched in the meta-analysis in the next month and so we are going to wait for the final results but I don’t think the main message will change.

Finally, the third important study in the early setting is for patients with triple negative breast cancer. In this regard we had a presentation of a study by the GEICAM group, so our Spanish colleagues, a randomised trial in which triple negative breast cancer patients that received standard adjuvant chemotherapy with anthracycline and taxane chemotherapy, after this treatment were randomised to receive capecitabine for either a few months, a few cycles, or normal treatment as per standard of care. The main message from this study – no difference between the two treatment arms so no benefit of extending the chemotherapy treatment with an additional agent which is capecitabine.

So these results are actually in the opposite direction as the findings from another very important study that was published a few months ago in The New England Journal of Medicine, the CREATE-X trial, in which the authors showed that using capecitabine in triple negative breast cancer patients after standard adjuvant chemotherapy is of benefit. However, to understand why these opposite results we have to go back to the patient population included in these two studies and this is what we have to do in our clinic to counsel our women on the importance or not to receive this additional chemotherapy. In the CREATE-X trial all patients, the patients that were included in the study, were women that received neoadjuvant chemotherapy and did not optimally respond to the treatment, so had residual disease after neoadjuvant chemotherapy, so a kind of high risk patient population. On the contrary, in the GEICAM study most of the patients received adjuvant chemotherapy, 55% were node negative, so a low risk patient population as compared to the CREATE-X study. The main message is that capecitabine remains a possible treatment to be discussed with our patients but only with those at high risk of disease recurrence, like women that do not respond to neoadjuvant anthracycline taxane based chemotherapy, but for women at low risk of disease recurrence, like receiving adjuvant chemotherapy, node negative, capecitabine should not be considered even in the case of triple negative breast cancer.