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Short-term adjuvant therapy fails to improve DFS in HER-2-positive breast cancer
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SAN ANTONIO — Women with early-stage HER-2-positive breast cancer who received 9 weeks of adjuvant trastuzumab and standard chemotherapy did not experience a DFS benefit comparable to women who received the adjuvant therapy for the standard duration of 1 year, according to data from the phase 3 SOLD clinical trial presented at the San Antonio Breast Cancer Symposium.
“The choice for 1-year duration of trastuzumab [Herceptin, Genentech] administration in patients with HER-2-positive breast cancer was arbitrary, and not based on research data,” Heikki Joensuu, MD, professor in the department of oncology at Helsinki University Hospital and University of Helsinki in Finland, said during a press briefing. “In the randomized trials that later established the current standard treatment regimen of chemotherapy plus trastuzumab, trastuzumab was given for 1 year. Thus, the 1-year duration became the standard.”
In the current phase 3 trial, Joensuu and colleagues assessed whether a shorter, 9-week duration of trastuzumab plus chemotherapy appeared comparable to the standard regimen of trastuzumab given during chemotherapy for 9 weeks and then as a single agent after stopping chemotherapy for 1 year.
The study cohort included 2,176 women (median age, 56 years) with early-stage HER-2-positive breast cancer and WHO performance status of 0 or 1, a node-positive or node-negative cancer larger than 5 mm, and left ventricle ejection fractions (LVEF) less than 50%.
Between January 2008 and December 2014, the researchers randomly assigned women 1:1 to 9 weeks or 1 year of trastuzumab. All patients received three cycles of either 80 mg/m² or 100 mg/m² docetaxel plus trastuzumab, three-times weekly followed by three cycles of chemotherapy. Patients in the 9-week arm received no additional treatment, whereas patients in the 1-year arm received trastuzumab every 3 weeks for 14 cycles.
After median follow-up of 5.2 years, DFS was 90.5% in the 1-year treatment arm vs. 88% in the 9-week treatment arm (HR = 1.39; 90% CI, 1.12-1.72).
However, 5-year distant DFS and OS were comparable between the two arms — 5-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 1-year arm (HR = 1.24; 90% CI, 0.93-1.65); 5-year OS was 94.7% in the 9-week arm vs. 95.9% in the 1-year arm (HR = 1.36; 90% CI, 0.98-1.89).
In a predefined subgroup analysis based on docetaxel dose, the DFS rate among patients who received 80 mg/m² docetaxel was 91.3% among those in the 1-year trastuzumab arm vs. 86.8% in the 9-week arm (HR = 1.66; 90% CI, 1.3-2.11; P interaction = .007). No significant differences were observed between the two arms with the 100-mg/m² docetaxel dose.
Congestive heart failure occurred among 3% of patients in the 1-year arm and 2% in the 9-week arm (P = .046). Patients in the 9-week arm had better maintained LVEF (P < .001).
Joensuu noted several limitations of the study, including not being able to reach the planned number of DFS events within a reasonable time frame. Also, the study had lower statistical power than planned. – by Jennifer Southall
Reference:
Joensuu H, et al. Abstract GS3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: The study was funded by Pharmac (New Zealand), Sanofi, Novartis, the Academy of Finland, the Cancer Society of Finland, Helsinki University Hospital research funds, Sigrid Juselius Foundation, and Jane and Aatos Erkko Foundation. Joensuu reports serving as a scientific advisor for Neutron Therapeutics; a consultant role with Orion Pharma; and owning stock in Orion Pharma, Faron Pharmaceuticals and Sartar Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Dawn L. Hershman, MD, MS
The study by Joensuu and colleagues confirmed that, overall, patients benefit from the full year of trastuzumab. However, like everything in oncology, the magnitude of the incremental benefit is related to the patient’s risk for recurrence. For low-risk patients, or patients who start to develop side effects, we can feel reassured that scaling back may still provide some benefit.
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