Trastuzumab Survival Gains Demonstrated By 11-Year HERA Follow-Up

medwireNews: Final efficacy analysis of the HERA trial confirms significant survival benefits for women with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer who receive 1 year of trastuzumab therapy after completion of primary treatment.

After a median follow-up of 11 years, the HERceptin Adjuvant (HERA) investigators report that a 1-year course of trastuzumab (8 mg/kg intravenously followed by 6 mg/kg every 3 weeks) significantly improved disease-free survival (DFS) and overall survival, with hazard ratios (HRs) of 0.76 and 0.74, respectively, compared with observation.

Extending trastuzumab therapy to 2 years did not provide additional survival benefits, however, say David Cameron, from the University of Edinburgh in the UK, and co-authors in The Lancet.

Subgroup analysis by hormone receptor status suggest this factor “remains a powerful determinant of disease outcome”, the researchers say, finding that the 10-year DFS rate was significantly lower in hormone receptor-positive than -negative patients whether they were treated with 1-year of trastuzumab (67 vs 72%) or observation (59 vs 66%).

And while DFS events were more common initially in hormone receptor-negative patients than their hormone receptor-positive counterparts, the DFS benefit “stabilised” at about 4 years regardless of hormone receptor status, they observe, “suggesting a substantial and permanent effect of 1 year of trastuzumab on micrometastatic disease.”

Moreover, trastuzumab efficacy was comparable in hormone receptor-negative and -positive patients, with the numerical difference in HRs not reaching clinical significance (HR=0.73 and 0.80 for 1 year of trastuzumab vs observation, respectively).

Trastuzumab efficacy was also unaffected by other tumour factors such as nodal status, “although the absolute benefits for an individual do depend on their underlying risk of recurrence after other standard therapies,” the HERA investigators explain.

Ten-year survival in the intention-to-treat group was estimated to be 69% for the 1702 patients in the 1-year trastuzumab arm of the trial and the 1700 participants given 2 years of the agent versus 63% for 1697 patients who were observed only.

Jennifer Specht and Nancy Davidson, both from the Fred Hutchinson Cancer Center in Seattle, Washington, USA, congratulate the authors in a linked comment for their “comprehensive analysis”, acknowledging that the “reported benefit of trastuzumab is probably underestimated” because 52% of patients crossed over from observation to treatment after the trial’s initial report in 2005.

“These findings support the current practice of adjuvant trastuzumab administration for 1 year and provide reassurance about its safety”, they add, observing that 10-year monitoring of secondary cardiac side effects gave an incidence of 4.4% and 7.3% for patients given 1 or 2 years of trastuzumab versus 0.9% with observation.

But acknowledging that the estimated absolute benefit with trastuzumab at 12 years is just 7% with a relapse rate of 30%, the team highlights research assessing the use of trastuzumab alongside taxane-based chemotherapy and other strategies to maximise trastuzumab benefits, such as combination therapy with pertuzumab in the APHINTY trial.

“[F]uture efforts to optimise therapy for patients with HER2-positive breast cancer will benefit

from identification of biomarkers (other than HER2 expression) that match patients and tumours to the most effective therapy”, the commentators conclude.

“Creative trials incorporating biospecimen collection before, during, and after therapy, coupled with strong correlative science studies which capture, analyse, or image tissue samples or blood biomarkers, will be key to improve outcomes for patients in the era of precision medicine.”

References

Cameron D, Piccart-Gebhart J, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet; Advance online publication 16 February 2017. http://dx.doi.org/10.1016/S0140-6736(16)32616-2

Specht JM, Davidson NE. Optimal duration for trastuzumab for early HER2-positive breast cancer. Lancet; Advance online publication 16 February 2017. DOI: http://dx.doi.org/10.1016/S0140-6736(17)30322-7 

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