HER2 Support Group Forums - View Single Post - subcutaneouss herceptin just as effective, safe as IV herceptin

Lani · 05-29-2019, 06:51 AM

JAMAOncology | BriefReport
Subcutaneous vs Intravenous Trastuzumab for Patients
With ERBB2-Positive Early Breast Cancer
Final Analysis of the HannaH Phase 3 Randomized Clinical Trial
Christian Jackisch, MD, PhD; Daniil Stroyakovskiy, MD; Xavier Pivot, MD; Jin Seok Ahn, MD; Bohuslav Melichar, MD, PhD; Shin-Cheh Chen, MD; Christoph Meyenberg, MSc; Nedal Al-Sakaff, PhD; Dominik Heinzmann, PhD; Roberto Hegg, MD, PhD

Author Affiliations: Author affiliations are listed at the end of this article.
Corresponding Author: Christian Jackisch, MD, PhD, Department of Obstetrics and Gynecology, Sana Klinikum Offenbach GmbH, Starkenburgring 66, D-63069 Offenbach, Germany (christian. jackisch@sana.de).
(Reprinted) 1/5

IMPORTANCE Confirmation of long-term comparability between subcutaneous and intravenous trastuzumab is essential.
OBJECTIVE Toevaluateefficacyandsafetyofsubcutaneoustrastuzum abcomparedwiththat of intravenous trastuzumab for patients with ERBB2 (HER2)–positive early breast cancer after 6 years’ follow-up in the HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial.
DESIGN,SETTING,ANDPARTICIPANTS Open-label,prospective,multicenter,international, neoadjuvant-adjuvant, randomized, phase 3 noninferiority clinical trial (primary end points: pathologic complete response and serum trough concentration predose cycle 8) conducted for 596 patients with ERBB2-positive early breast cancer enrolled from October 19, 2009, to December 1, 2010.
INTERVENTIONS Eligiblepatientsreceived8cyclesofchemotherapy(4cyc lesofdocetaxel, 75 mg/m2, followed by 4 cycles of fluorouracil, 500 mg/m2, epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) with either fixed-dose subcutaneous trastuzumab, 600 mg, or intravenous trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in the neoadjuvant setting. Patients received an additional 10 cycles of subcutaneous trastuzumab or intravenous trastuzumab (according to their initial randomization) after surgery in the adjuvant setting to complete 1 year of anti-ERBB2 therapy.
MAINOUTCOMESANDMEASURES Event-freeandoverallsurvivalrateswerecalculatedusing the Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazards regression. Adverse events and serious adverse events were graded per standard criteria.
RESULTS Intotal,294women(mean[SD]age,50.3[11.1]years)treatedwithsubcutaneous trastuzumab and 297 women (mean [SD] age, 49.5 [10.8] years) treated with intravenous trastuzumab were included in respective intention-to-treat populations. Six-year event-free survival rates (65% in both study groups; hazard ratio, 0.98; 95% CI, 0.74-1.29) and overall survival rates (84% in both study groups; hazard ratio, 0.94; 95% CI, 0.61-1.45) were similar between the subcutaneous and intravenous trastuzumab groups. Patients achieving a total pathologic complete response had longer event-free survival and higher 6-year overall survival rates than those with residual disease. Incidence of adverse events (290 of 297 [97.6%] vs 282 of 298 [94.6%]), grade 3 or higher adverse events (158 of 297 [53.2%] vs 160 of 298 [53.7%]), cardiac events (44 of 297 [14.8%] vs 42 of 298 [14.1%]), and serious adverse events (65 of 297 [21.9%] vs 45 of 298 [15.1%]) was comparable between the subcutaneous and intravenous trastuzumab treatment groups.
CONCLUSIONSANDRELEVANCE ThisfinalanalysisoftheHannaHtrialfurtherconfirmsth e comparable efficacy and safety of subcutaneous and intravenous trastuzumab and highlights the suitability of subcutaneous trastuzumab as an alternative route of administration for
patients with ERBB2-positive early breast cancer. TRIALREGISTRATION ClinicalTrials.govidentifier:NCT00950300
JAMA Oncol. 2019;5(5):e190339. doi:10.1001/jamaoncol.2019.0339 Published online April 18, 2019.

05-29-2019, 06:51 AM	#1
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	subcutaneouss herceptin just as effective, safe as IV herceptin JAMAOncology \| BriefReport Subcutaneous vs Intravenous Trastuzumab for Patients With ERBB2-Positive Early Breast Cancer Final Analysis of the HannaH Phase 3 Randomized Clinical Trial Christian Jackisch, MD, PhD; Daniil Stroyakovskiy, MD; Xavier Pivot, MD; Jin Seok Ahn, MD; Bohuslav Melichar, MD, PhD; Shin-Cheh Chen, MD; Christoph Meyenberg, MSc; Nedal Al-Sakaff, PhD; Dominik Heinzmann, PhD; Roberto Hegg, MD, PhD Author Affiliations: Author affiliations are listed at the end of this article. Corresponding Author: Christian Jackisch, MD, PhD, Department of Obstetrics and Gynecology, Sana Klinikum Offenbach GmbH, Starkenburgring 66, D-63069 Offenbach, Germany (christian. jackisch@sana.de). (Reprinted) 1/5 IMPORTANCE Confirmation of long-term comparability between subcutaneous and intravenous trastuzumab is essential. OBJECTIVE Toevaluateefficacyandsafetyofsubcutaneoustrastuzum abcomparedwiththat of intravenous trastuzumab for patients with ERBB2 (HER2)–positive early breast cancer after 6 years’ follow-up in the HannaH (Enhanced Treatment With Neoadjuvant Herceptin) trial. DESIGN,SETTING,ANDPARTICIPANTS Open-label,prospective,multicenter,international, neoadjuvant-adjuvant, randomized, phase 3 noninferiority clinical trial (primary end points: pathologic complete response and serum trough concentration predose cycle 8) conducted for 596 patients with ERBB2-positive early breast cancer enrolled from October 19, 2009, to December 1, 2010. INTERVENTIONS Eligiblepatientsreceived8cyclesofchemotherapy(4cyc lesofdocetaxel, 75 mg/m2, followed by 4 cycles of fluorouracil, 500 mg/m2, epirubicin, 75 mg/m2, and cyclophosphamide, 500 mg/m2) with either fixed-dose subcutaneous trastuzumab, 600 mg, or intravenous trastuzumab (loading dose, 8 mg/kg; maintenance dose, 6 mg/kg) every 3 weeks in the neoadjuvant setting. Patients received an additional 10 cycles of subcutaneous trastuzumab or intravenous trastuzumab (according to their initial randomization) after surgery in the adjuvant setting to complete 1 year of anti-ERBB2 therapy. MAINOUTCOMESANDMEASURES Event-freeandoverallsurvivalrateswerecalculatedusing the Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazards regression. Adverse events and serious adverse events were graded per standard criteria. RESULTS Intotal,294women(mean[SD]age,50.3[11.1]years)treatedwithsubcutaneous trastuzumab and 297 women (mean [SD] age, 49.5 [10.8] years) treated with intravenous trastuzumab were included in respective intention-to-treat populations. Six-year event-free survival rates (65% in both study groups; hazard ratio, 0.98; 95% CI, 0.74-1.29) and overall survival rates (84% in both study groups; hazard ratio, 0.94; 95% CI, 0.61-1.45) were similar between the subcutaneous and intravenous trastuzumab groups. Patients achieving a total pathologic complete response had longer event-free survival and higher 6-year overall survival rates than those with residual disease. Incidence of adverse events (290 of 297 [97.6%] vs 282 of 298 [94.6%]), grade 3 or higher adverse events (158 of 297 [53.2%] vs 160 of 298 [53.7%]), cardiac events (44 of 297 [14.8%] vs 42 of 298 [14.1%]), and serious adverse events (65 of 297 [21.9%] vs 45 of 298 [15.1%]) was comparable between the subcutaneous and intravenous trastuzumab treatment groups. CONCLUSIONSANDRELEVANCE ThisfinalanalysisoftheHannaHtrialfurtherconfirmsth e comparable efficacy and safety of subcutaneous and intravenous trastuzumab and highlights the suitability of subcutaneous trastuzumab as an alternative route of administration for patients with ERBB2-positive early breast cancer. TRIALREGISTRATION ClinicalTrials.govidentifier:NCT00950300 JAMA Oncol. 2019;5(5):e190339. doi:10.1001/jamaoncol.2019.0339 Published online April 18, 2019.