Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer

Potential predictive relationship with tumor HER2 activation status

Michael S. Gordon, Daniela Matei, Carol Aghajanian, Ursula A. Matulonis, Molly Brewer, Gini F. Fleming, John D. Hainsworth, Agustin A. Garcia, Mark D. Pegram, Russell J. Schilder, David E. Cohn, Lynda Roman, Mika K. Derynck, Kimmie Ng, Benjamin Lyons, David E. Allison, David A. Eberhard, Thinh Q. Pham, Randall C. Dere, Beth Y. Karlan

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Purpose: Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC. Patients and Methods: Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2). Results: Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD ≥ 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2-(n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility). Conclusion: Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.

Original languageEnglish (US)
Pages (from-to)4324-4332
Number of pages9
JournalJournal of Clinical Oncology
Volume24
Issue number26
DOIs
StatePublished - Sep 10 2006
Externally publishedYes

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Dimerization
Ovarian Neoplasms
Neoplasms
Disease-Free Survival
pertuzumab
Enzyme-Linked Immunosorbent Assay
Biopsy
Antibodies, Monoclonal, Humanized
Gene Amplification
Stroke Volume
Multicenter Studies
Diarrhea
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer : Potential predictive relationship with tumor HER2 activation status. / Gordon, Michael S.; Matei, Daniela; Aghajanian, Carol; Matulonis, Ursula A.; Brewer, Molly; Fleming, Gini F.; Hainsworth, John D.; Garcia, Agustin A.; Pegram, Mark D.; Schilder, Russell J.; Cohn, David E.; Roman, Lynda; Derynck, Mika K.; Ng, Kimmie; Lyons, Benjamin; Allison, David E.; Eberhard, David A.; Pham, Thinh Q.; Dere, Randall C.; Karlan, Beth Y.

In: Journal of Clinical Oncology, Vol. 24, No. 26, 10.09.2006, p. 4324-4332.

Research output: Contribution to journalArticle

Gordon, MS, Matei, D, Aghajanian, C, Matulonis, UA, Brewer, M, Fleming, GF, Hainsworth, JD, Garcia, AA, Pegram, MD, Schilder, RJ, Cohn, DE, Roman, L, Derynck, MK, Ng, K, Lyons, B, Allison, DE, Eberhard, DA, Pham, TQ, Dere, RC & Karlan, BY 2006, 'Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer: Potential predictive relationship with tumor HER2 activation status', Journal of Clinical Oncology, vol. 24, no. 26, pp. 4324-4332. https://doi.org/10.1200/JCO.2005.05.4221
Gordon, Michael S. ; Matei, Daniela ; Aghajanian, Carol ; Matulonis, Ursula A. ; Brewer, Molly ; Fleming, Gini F. ; Hainsworth, John D. ; Garcia, Agustin A. ; Pegram, Mark D. ; Schilder, Russell J. ; Cohn, David E. ; Roman, Lynda ; Derynck, Mika K. ; Ng, Kimmie ; Lyons, Benjamin ; Allison, David E. ; Eberhard, David A. ; Pham, Thinh Q. ; Dere, Randall C. ; Karlan, Beth Y. / Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer : Potential predictive relationship with tumor HER2 activation status. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 26. pp. 4324-4332.
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abstract = "Purpose: Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC. Patients and Methods: Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2). Results: Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3{\%}; 95{\%} CI, 1.7{\%} to 9.4{\%}), eight patients (6.8{\%}) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50{\%} (includes two partial responses and four patients with SD ≥ 6 months; total clinical activity, 14.5{\%}). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6{\%}) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2-(n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1{\%} (11.4{\%} grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50{\%} (one confirmed by central facility). Conclusion: Pertuzumab is well tolerated with a RR of 4.3{\%} in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.",
author = "Gordon, {Michael S.} and Daniela Matei and Carol Aghajanian and Matulonis, {Ursula A.} and Molly Brewer and Fleming, {Gini F.} and Hainsworth, {John D.} and Garcia, {Agustin A.} and Pegram, {Mark D.} and Schilder, {Russell J.} and Cohn, {David E.} and Lynda Roman and Derynck, {Mika K.} and Kimmie Ng and Benjamin Lyons and Allison, {David E.} and Eberhard, {David A.} and Pham, {Thinh Q.} and Dere, {Randall C.} and Karlan, {Beth Y.}",
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T1 - Clinical activity of pertuzumab (rhuMAb 2C4), a HER dimerization inhibitor, in advanced ovarian cancer

T2 - Potential predictive relationship with tumor HER2 activation status

AU - Gordon, Michael S.

AU - Matei, Daniela

AU - Aghajanian, Carol

AU - Matulonis, Ursula A.

AU - Brewer, Molly

AU - Fleming, Gini F.

AU - Hainsworth, John D.

AU - Garcia, Agustin A.

AU - Pegram, Mark D.

AU - Schilder, Russell J.

AU - Cohn, David E.

AU - Roman, Lynda

AU - Derynck, Mika K.

AU - Ng, Kimmie

AU - Lyons, Benjamin

AU - Allison, David E.

AU - Eberhard, David A.

AU - Pham, Thinh Q.

AU - Dere, Randall C.

AU - Karlan, Beth Y.

PY - 2006/9/10

Y1 - 2006/9/10

N2 - Purpose: Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC. Patients and Methods: Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2). Results: Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD ≥ 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2-(n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility). Conclusion: Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.

AB - Purpose: Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC. Patients and Methods: Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2). Results: Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD ≥ 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2-(n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility). Conclusion: Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.

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