Subcutaneous Pertuzumab Plus Trastuzumab Shows Comparable 4-Year Outcomes to Intravenous Therapy in HER2-Positive Breast Cancer

Clinical Summary:

• Design/Population: The phase 3 FeDeriCa compared a fixed-dose subcutaneous combination of pertuzumab plus trastuzumab with intravenous pertuzumab plus trastuzumab in patients with HER2-positive operable, locally advanced, or inflammatory stage II to IIIC breast cancer.
• Key Outcomes: At approximately 4 years of follow-up, long-term invasive disease-free survival, event-free survival, distant recurrence-free interval, and overall survival were comparable between treatment groups. No new safety signals, including cardiac safety signals, emerged. 
• Clinical Relevance: Findings support fixed-dose subcutaneous pertuzumab plus trastuzumab as a clinically comparable alternative to intravenous pertuzumab plus trastuzumab that substantially shortens administration time and reduced the burden associated with prolonged intravenous treatment.

Long-term results from the phase 3 FeDeriCa trial showed that the fixed-dose subcutaneous  pertuzumab plus trastuzumab maintained efficacy comparable with intravenous pertuzumab plus trastuzumab in patients with HER2-positive early breast cancer, supporting the less invasive formulation as a convenient alternative without compromising long-term outcomes. 

“The logistical and physical burdens of prolonged [intravenous] infusions—particularly in curative-intent settings where patients may receive up to 18 cycles of therapy—have highlighted the need for more convenient, less invasive treatment approaches that align with patient preferences and optimize health care resource use,” stated Christian Jackisch, MD, PhD, Varisano Clinic Frankfurt Hoechst, Frankfurt, Germany, and coauthors. “Administration via [subcutaneous] injection reduces the burden and time that patients spend in infusion chairs and has the potential to optimize the use of medical resources.” 

In this trial, researchers enrolled 500 patients with HER2-positive operable, locally advanced, or inflammatory stage II to IIIC breast cancer with tumors larger than 2 cm or node-positive disease. Patients were randomized 1:1 to receive 8 cycles of neoadjuvant chemotherapy with either intravenous (n = 252) or fixed-dose subcutaneous (n = 248) pertuzumab plus trastuzumab every 3 weeks during cycles 5 through 8, followed by surgery and continued HER2-targeted treatment according to randomization to complete 18 cycles. 

Intravenous treatment consisted of an 840 mg loading dose of pertuzumab followed by 420 mg, plus 8 mg/kg of trastuzumab followed by 6 mg/kg. The fixed-dose subcutaneous regimen consisted of a loading dose of 1200 mg of pertuzumab plus 600 mg of trastuzumab, followed by 600 mg of each agent. Key end points included invasive disease-free survival (iDFS), event-free survival (EFS), distant recurrence-free interval, overall survival (OS), and safety. 

At data cutoff, median follow-up was 51.4 months in the intravenous arm and 51.2 months in the fixed-dose subcutaneous arm. The 4-year iDFS rates were 89.6 and 88.5%, respectively, and the 4-year EFS rates were 88.5% and 86.6%. 

Long-term outcomes were also similar for distant disease control and survival. The 4-year distant recurrence-free survival rate was 92.5% in the intravenous arm and 91.9% in the fixed-dose subcutaneous arm. The 4-year OS rates were 95.5% and 94.1%, respectively. Investigators noted that the study was not statistically powered to detect significant differences in these long-term efficacy end points. 

Long-term safety remained generally similar between treatment groups, with no new safety signals identified. Grade ≥3 adverse events occurred in 59.1% of patients in the intravenous arm and 53.2% of patients in the fixed-dose subcutaneous arm. Serious adverse events occurred in 20.6% and 19.8% of patients, respectively. Injection-site reactions were more frequent with subcutaneous treatment, occurring in 13.3% of patients compared with 0.4% in the intravenous arm.

Cardiac events remained uncommon and no new cardiac safety signals were identified. During the adjuvant phase, New York Heart Association class 3/4 heart failure accompanied by a decrease in left ventricular ejection fraction of at least 10 percentage points from baseline to less than 50% occurred in 1 patient receiving intravenous treatment and 2 patients receiving fixed-dose subcutaneous treatment. 

“The results obtained in this final analysis of the FeDeriCa study complement, in a long-term analysis, the results obtained in the primary analysis,” concluded Dr Jackisch et al. Fixed-dose subcutaneous pertuzumab plus trastuzumab “is established as a faster, more convenient, less invasive patient- and health care professional-preferred alternative… and reduces the cost and waste involved in treatment.”

Source:

Jackisch C, Im SA, Mattar A, et al. Final analysis of the FeDeriCa phase III study: Long-term efficacy, safety and pharmacokinetics of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection, plus chemotherapy, in HER2-positive early breast cancer. ESMO Open. Published online: July 31, 2026. doi: 10.1016/j.esmoop.2026.108328