Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer

Sharmila K. Makhija, Lukas C. Amler, Dana Glenn, Frederick R. Ueland, Michael A. Gold, Don S. Dizon, Virginia Paton, Chin Yu Lin, Thomas Januario, Kimmie Ng, Andreas Strauss, Stephen Kelsey, Mark X. Sliwkowski, Ursula Matulonis

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Purpose: Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. Patients and Methods: Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. Results: One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. Conclusion: Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.

Original languageEnglish (US)
Pages (from-to)1215-1223
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number7
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

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gemcitabine
Fallopian Tube Neoplasms
Platinum
Ovarian Neoplasms
Neoplasms
Disease-Free Survival
pertuzumab
Placebos
Antibodies, Monoclonal, Humanized
Messenger RNA
Fallopian Tubes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. / Makhija, Sharmila K.; Amler, Lukas C.; Glenn, Dana; Ueland, Frederick R.; Gold, Michael A.; Dizon, Don S.; Paton, Virginia; Lin, Chin Yu; Januario, Thomas; Ng, Kimmie; Strauss, Andreas; Kelsey, Stephen; Sliwkowski, Mark X.; Matulonis, Ursula.

In: Journal of Clinical Oncology, Vol. 28, No. 7, 01.03.2010, p. 1215-1223.

Research output: Contribution to journalArticle

Makhija, SK, Amler, LC, Glenn, D, Ueland, FR, Gold, MA, Dizon, DS, Paton, V, Lin, CY, Januario, T, Ng, K, Strauss, A, Kelsey, S, Sliwkowski, MX & Matulonis, U 2010, 'Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer', Journal of Clinical Oncology, vol. 28, no. 7, pp. 1215-1223. https://doi.org/10.1200/JCO.2009.22.3354
Makhija, Sharmila K. ; Amler, Lukas C. ; Glenn, Dana ; Ueland, Frederick R. ; Gold, Michael A. ; Dizon, Don S. ; Paton, Virginia ; Lin, Chin Yu ; Januario, Thomas ; Ng, Kimmie ; Strauss, Andreas ; Kelsey, Stephen ; Sliwkowski, Mark X. ; Matulonis, Ursula. / Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 7. pp. 1215-1223.
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abstract = "Purpose: Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. Patients and Methods: Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. Results: One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95{\%} CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8{\%} in patients who received gemcitabine + pertuzumab compared with 4.6{\%} in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95{\%} CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. Conclusion: Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.",
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T1 - Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer

AU - Makhija, Sharmila K.

AU - Amler, Lukas C.

AU - Glenn, Dana

AU - Ueland, Frederick R.

AU - Gold, Michael A.

AU - Dizon, Don S.

AU - Paton, Virginia

AU - Lin, Chin Yu

AU - Januario, Thomas

AU - Ng, Kimmie

AU - Strauss, Andreas

AU - Kelsey, Stephen

AU - Sliwkowski, Mark X.

AU - Matulonis, Ursula

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Purpose: Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer. Patients and Methods: Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting. Results: One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm. Conclusion: Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.

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