Combination targeted therapy without chemotherapy a good option for some HER2-positive breast cancer: study
19 Dec 2014
A new study in patients led by researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine supports a theory - which first started with animal studies in a Baylor laboratory 12 years ago - that a certain group of breast cancer patients with tumours that have the protein HER-2 (which can promote the growth of breast cancer) may benefit from a combination of targeted therapy and may not need chemotherapy.
The new phase II clinical trial results were reported at the San Antonio Breast Cancer Symposium.
Dr. Mothaffar Rimawi, medical director of the Smith Breast Center and the principal investigator of the study, presented the results of the study (TBCR023) orally on behalf of the Translational Breast Cancer Research Consortium.
The multi-center trial expanded on earlier studies conducted by Baylor investigators that showed that a combination of the targeted treatments lapatinib and trastuzumab, when given with endocrine therapy, and without chemotherapy, resulted in eradication of cancer in the breast and lymph nodes in some patients with HER-2 positive breast cancer, a subtype of the disease traditionally treated with aggressive chemotherapy and trastuzumab.
They first reported the results of this approach in 2013.
Translational research
''We first showed this favourable response to combination therapy in HER-2 positive tumours in mice,'' said Rimawi. ''We then translated these findings in human trials, showing that, in fact, this combination of anti-HER2 therapy for only 12 weeks showed an excellent response in humans without having to go through chemotherapy, an often grueling and toxic aspect of treatment.''
Rimawi and colleagues were eager to take the next steps. What happens if we double the duration of treatment time, they asked?
Rimawi had a hunch they would see even better results at least in those tumours that were HER-2 and estrogen receptor-positive, and he was right.
The finding was meaningful - the team observed a nearly doubled complete response with 24 weeks of treatment, meaning that all evidence of invasive cancer in the breast was gone at the time of surgery.
Study design
The trial followed 94 patients (between November 2011 and November 2013) with tumours 2 centimeters or larger; 33 were treated for 12 weeks like the original trial and 61 were treated for 24 weeks.
The average size of tumours was 5cm and a majority of the patients (65 per cent) also had tumours that grew when exposed to estrogen (ER-positive).
Both groups received lapatinib and trastuzumab plus the endocrine therapy letrozole (along with ovarian suppression in premenopausal women) if the tumor was also positive for the estrogen receptor.
Tumour biopsies were collected at baseline, after the first week, after 12 weeks, and again at time of surgery.
Results
In the 12-week group, the overall response was 12 percent while the 24-week group showed a 28 percent complete response with no evidence of tumor remaining in the breast.
Breaking down the results, the researchers showed that the ER-positive, 12-week group showed a 9 percent complete response versus 33 percent in the 24-week group, more than a three-fold difference.
The ER-negative, 12-week group showed a complete response rate of 20 per cent while the 24-week group showed an 18 per cent complete response, indicating that the longer treatment was better only in the HER-2 and estrogen receptor-positive group of patients.
The treatment was well tolerated in both groups with a mild skin rash and diarrhea being the most common side effects.
''This approach needs more clinical study before we can say that some patients can be treated safely with this approach and now we are focusing our research to more clearly define which women do and do not need chemotherapy,'' said Dr. Kent Osborne, director of the NCI-designated Dan L. Duncan Cancer Center at Baylor, and the co-director of the Symposium, and a collaborator on the study. ''This may spare some the cost and toxicity of chemotherapy.''
Rimawi initiated these studies while training as a fellow at Baylor in Osborne's and Rachel Schiff's lab.
Additional collaborators on the study include Polly Niravath, Tao Wang, Julie Nangia, Sao Jiralerspong, Anne Pavlick, Carolina Gutierrez, Rachel Schiff and Susan Hilsenbeck, all of Baylor; Brent Rexer of Vanderbilt University in Nashville, Tenn; Andres Forero of the University of Alabama in Birmingham; Antonio C Wolff of Johns Hopkins University in Baltimore, Md; Rita Nanda of the University of Chicago; Anna M Storniolo of Indiana University; Ian Krop of the Dana-Farber Cancer Institute in Boston and Matthew P Goetz of the Mayo Clinic in Rochester.
