Adding lapatinib to adjuvant trastuzumab does not improve outcomes in early- stage HER2-positive breast cancer

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Published: 1 Jun 2014
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Dr Edith Perez - Mayo Clinic, Rochester, USA

Dr Perez talks to ecancertv at ASCO 2014 about the findings from a large phase III study, ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) which suggest that post-surgery (adjuvant) treatment using a combination of two HER2-targeted drugs – trastuzumab and lapatinib – is no more effective than standard treatment with trastuzumab alone for women with early HER2-positive breast cancer.

Read the article or watch the press conference for more.

 

 

This study was for patients with resected or early stage HER2 positive breast cancer tumours. So specifically we wanted to test whether the standard of care currently, which is trastuzumab, would be improved by adding a second anti-HER2 therapy, so just lapatinib.

What did you do in your study?

What we did is that we conducted a prospective global trial with a lot of collaboration in which we assigned patients to receive the standard chemotherapy surgery and after that they could receive anti-HER2 therapy in the form of trastuzumab alone, trastuzumab followed by lapatinib or the concurrent or dual administration of the two anti-HER2 treatments.

What did you find?

It came out that lapatinib did not add to the benefit of trastuzumab. So in terms of efficacy we showed that trastuzumab should remain the standard of care anti-HER2 treatment for patients with HER2 positive breast cancer. We also found that this treatment was actually very safe, especially from the cardiac standpoint, as fewer than 1% of patients had any significant cardiac toxicity. This is very important for clinical practice.

What did you discover about the efficacy of these approaches?

The efficacy was much better than we had anticipated, more than 95% of the patients had a life after 4½ years of median follow-up and approximately 86% of the patients are alive without breast cancer. So it reflects the improvements we’re making in the field overall, it also lets us know that we need to do still some translational work to correlate some of the molecular findings in the tumours to identify the subgroup of patients who do so well with trastuzumab they don’t need anything else and other patients who may benefit from participation in new clinical trials.

What are the clinical implications that oncologists should take note of?

The clinical implications include that trastuzumab added to chemotherapy remains the standard of care globally for patients with HER2 positive breast cancer, also that this therapy is very safe from the cardiac standpoint. The last, but very important, finding from ALTTO for practice is that in ALTTO we could not corroborate that the dual anti-HER2 blockade, which had been predicted to lead to a better survival based on the results of the neoadjuvant study called NeoALTTO, could not be corroborated. So ALTTO really calls into question the concept that we could use the results of neoadjuvant studies to predict what happens in the most important setting, which is the adjuvant setting.

What do you make of using early markers of disease improvements in your findings?

This is a very important point because many people, including ourselves, we felt that the early surrogate of pathological complete response findings could explain or predict what would happen in the adjuvant setting. But unfortunately that is not the case and now this has been shown in patients with hormone receptor positive breast cancer, it has been shown with bevacizumab in patients with triple negative breast cancer where bevacizumab improves pathological complete response in triple negative but it does not improve disease free or overall survival in the adjuvant setting. Now we have the third subtype of breast cancer, HER2 positive breast cancer, in which we are showing the same thing. The findings in pathological CR do not appear to correlate with ultimate patient disease free or overall survival.

What is the take away message for doctors from this particular study?

The bottom line – lapatinib does not add to the benefit of trastuzumab; trastuzumab on its own leads to a much better outcome than we had anticipated and this therapy is very safe for patients.

What are the big areas of progress in breast cancer research generally?

In addition to these clinical results of drugs per se is the fact that we are finding molecular markers in the tumours that are helping us predict outcome of patients. Specifically, we did a presentation in which we have identified a fourteen gene profile that appears to correlate quite well to benefit to trastuzumab. I think that is really a hint of the future. We need to better understand biology and now that we’re getting the results to reach that point.

What advances in clinical practice should doctors be aware of?

That it’s important to collect tumour specimens; it’s important to share tumour specimens with investigators so that we can understand the underlying basis of breast cancer to develop better treatments.

What do you think of the breast cancer treatment for younger patients?

There are two different areas for young women diagnosed with breast cancer: number one, can we do something to help preserve fertility and some data were presented here at ASCO related to this issue. The other issue is how we should treat their cancer per se. So for some women in which physicians and the patient decide to proceed with ovarian function suppression then one of the presentations here at ASCO showed that using an aromatase inhibitor, specifically exemestane, led to better outcomes compared to Tamoxifen. But again, the central question which will be answered later this year is whether ovarian function suppression should be part of standard of care for premenopausal women with breast cancer.