Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma

Toshihiko Doi, Sarina A. Piha-Paul, Shadia Jalal, Sanatan Saraf, Jared Lunceford, Minori Koshiji, Jaafar Bennouna

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose The anti-programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)-positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1-positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate, determined by investigator review per Response Evaluation Criteria in Solid Tumors (version 1.1). Results Among 83 patientswith esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45%) had PD-L1-positive tumors, and 23 were enrolled. Median age was 65 years; 78% had squamous histology; and 87% received ≥ two prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months). Nine patients (39%) experienced treatment-related adverse events, mostcommonly decreased appetite, decreased lymphocyte count, generalized rash, and rash (two patients [9%] each). No grade 4 adverse events or deaths were attributed to pembrolizumab. Overall response rate was 30%(95%CI, 13%to 53%);median duration of response was 15months (range, 6 to 26months). A six-gene interferon-g gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumabtreated patients with higher interferon-g composite scores. Conclusion Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1-positive advanced esophageal carcinoma.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2018

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Carcinoma
Safety
Antibodies
Ligands
Exanthema
Interferons
Esophagogastric Junction
Neoplasms
Lymphocyte Count
Appetite
pembrolizumab
Transcriptome
Disease Progression
Squamous Cell Carcinoma
Histology
Therapeutics
Research Personnel
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. / Doi, Toshihiko; Piha-Paul, Sarina A.; Jalal, Shadia; Saraf, Sanatan; Lunceford, Jared; Koshiji, Minori; Bennouna, Jaafar.

In: Journal of Clinical Oncology, Vol. 36, No. 1, 01.01.2018, p. 61-67.

Research output: Contribution to journalArticle

Doi, Toshihiko ; Piha-Paul, Sarina A. ; Jalal, Shadia ; Saraf, Sanatan ; Lunceford, Jared ; Koshiji, Minori ; Bennouna, Jaafar. / Safety and antitumor activity of the anti-programmed death-1 antibody pembrolizumab in patients with advanced esophageal carcinoma. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 1. pp. 61-67.
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abstract = "Purpose The anti-programmed death-1 antibody pembrolizumab was evaluated in KEYNOTE-028, a multicohort, phase IB study of patients with programmed death ligand-1 (PD-L1)-positive advanced solid tumors. Results from the esophageal carcinoma cohort are reported herein. Patients and Methods Eligible patients with squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction in whom standard therapy failed and who had PD-L1-positive tumors received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed disease progression or intolerable toxicity. Response was assessed every 8 weeks up to 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate, determined by investigator review per Response Evaluation Criteria in Solid Tumors (version 1.1). Results Among 83 patientswith esophageal carcinoma and samples evaluable for PD-L1 expression, 37 (45{\%}) had PD-L1-positive tumors, and 23 were enrolled. Median age was 65 years; 78{\%} had squamous histology; and 87{\%} received ≥ two prior therapies for advanced/metastatic disease. As of the data cutoff (February 20, 2017), median follow-up was 7 months (range, 1 to 33 months). Nine patients (39{\%}) experienced treatment-related adverse events, mostcommonly decreased appetite, decreased lymphocyte count, generalized rash, and rash (two patients [9{\%}] each). No grade 4 adverse events or deaths were attributed to pembrolizumab. Overall response rate was 30{\%}(95{\%}CI, 13{\%}to 53{\%});median duration of response was 15months (range, 6 to 26months). A six-gene interferon-g gene expression signature analysis suggested that delayed progression and increased response occur among pembrolizumabtreated patients with higher interferon-g composite scores. Conclusion Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1-positive advanced esophageal carcinoma.",
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AU - Piha-Paul, Sarina A.

AU - Jalal, Shadia

AU - Saraf, Sanatan

AU - Lunceford, Jared

AU - Koshiji, Minori

AU - Bennouna, Jaafar

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