Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma

Bert H. O’Neil, John M. Wallmark, David Lorente, Elena Elez, Judith Raimbourg, Carlos Gomez-Roca, Samuel Ejadi, Sarina A. Piha-Paul, Mark N. Stein, Albiruni R. Abdul Razak, Katia Dotti, Armando Santoro, Roger B. Cohen, Marlena Gould, Sanatan Saraf, Karen Stein, Sae Won Han

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Abstract

Background Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti–PD-1 antibody pembrolizumab was evaluated in 20 PD-L1–positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. Methods Patients with advanced, treatment-resistant PD-L1–positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate by investigator review per Response Evaluation Criteria in Solid Tumors version 1.1. Data cutoff was June 20, 2016. Results Of 137 patients with CRC and samples evaluable for PD-L1 expression, 33 (24%) had PD-L1–positive tumors, of which 23 were enrolled. Median follow-up was 5.3 months, and 8 patients (35%) reported treatment-related adverse events (AEs), most commonly fatigue (n = 3, 13%), stomatitis (n = 2, 9%), and asthenia (n = 2, 9%). One patient (4%) experienced grade 4 treatment-related increased blood bilirubin. No grade 3 AEs, discontinuations, or deaths were attributed to treatment. Most patients (n = 15, 65%) experienced progressive disease. One partial response occurred in a patient (4%) with MSI-high CRC. Conclusion Pembrolizumab demonstrated a favorable safety profile in advanced PD-L1–positive CRC. Antitumor activity was observed in a single patient with MSI-high CRC, warranting further evaluation in this patient population.
Original languageEnglish
JournalPLoS One
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

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colorectal neoplasms
Microsatellite Repeats
Tumors
Colorectal Neoplasms
Safety
antibodies
Antibodies
Microsatellite Instability
Ligands
Bilirubin
Toxicity
Blood
microsatellite repeats
death
Fatigue of materials
neoplasms
Asthenia
Stomatitis
pembrolizumab
bilirubin

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O’Neil, B. H., Wallmark, J. M., Lorente, D., Elez, E., Raimbourg, J., Gomez-Roca, C., ... Han, S. W. (2017). Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PLoS One, 12(12). https://doi.org/10.1371/journal.pone.0189848

Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. / O’Neil, Bert H.; Wallmark, John M.; Lorente, David; Elez, Elena; Raimbourg, Judith; Gomez-Roca, Carlos; Ejadi, Samuel; Piha-Paul, Sarina A.; Stein, Mark N.; Abdul Razak, Albiruni R.; Dotti, Katia; Santoro, Armando; Cohen, Roger B.; Gould, Marlena; Saraf, Sanatan; Stein, Karen; Han, Sae Won.

In: PLoS One, Vol. 12, No. 12, 01.12.2017.

Research output: Contribution to journalArticle

O’Neil, BH, Wallmark, JM, Lorente, D, Elez, E, Raimbourg, J, Gomez-Roca, C, Ejadi, S, Piha-Paul, SA, Stein, MN, Abdul Razak, AR, Dotti, K, Santoro, A, Cohen, RB, Gould, M, Saraf, S, Stein, K & Han, SW 2017, 'Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma', PLoS One, vol. 12, no. 12. https://doi.org/10.1371/journal.pone.0189848
O’Neil, Bert H. ; Wallmark, John M. ; Lorente, David ; Elez, Elena ; Raimbourg, Judith ; Gomez-Roca, Carlos ; Ejadi, Samuel ; Piha-Paul, Sarina A. ; Stein, Mark N. ; Abdul Razak, Albiruni R. ; Dotti, Katia ; Santoro, Armando ; Cohen, Roger B. ; Gould, Marlena ; Saraf, Sanatan ; Stein, Karen ; Han, Sae Won. / Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. In: PLoS One. 2017 ; Vol. 12, No. 12.
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abstract = "Background Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti–PD-1 antibody pembrolizumab was evaluated in 20 PD-L1–positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. Methods Patients with advanced, treatment-resistant PD-L1–positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate by investigator review per Response Evaluation Criteria in Solid Tumors version 1.1. Data cutoff was June 20, 2016. Results Of 137 patients with CRC and samples evaluable for PD-L1 expression, 33 (24{\%}) had PD-L1–positive tumors, of which 23 were enrolled. Median follow-up was 5.3 months, and 8 patients (35{\%}) reported treatment-related adverse events (AEs), most commonly fatigue (n = 3, 13{\%}), stomatitis (n = 2, 9{\%}), and asthenia (n = 2, 9{\%}). One patient (4{\%}) experienced grade 4 treatment-related increased blood bilirubin. No grade 3 AEs, discontinuations, or deaths were attributed to treatment. Most patients (n = 15, 65{\%}) experienced progressive disease. One partial response occurred in a patient (4{\%}) with MSI-high CRC. Conclusion Pembrolizumab demonstrated a favorable safety profile in advanced PD-L1–positive CRC. Antitumor activity was observed in a single patient with MSI-high CRC, warranting further evaluation in this patient population.",
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AU - O’Neil, Bert H.

AU - Wallmark, John M.

AU - Lorente, David

AU - Elez, Elena

AU - Raimbourg, Judith

AU - Gomez-Roca, Carlos

AU - Ejadi, Samuel

AU - Piha-Paul, Sarina A.

AU - Stein, Mark N.

AU - Abdul Razak, Albiruni R.

AU - Dotti, Katia

AU - Santoro, Armando

AU - Cohen, Roger B.

AU - Gould, Marlena

AU - Saraf, Sanatan

AU - Stein, Karen

AU - Han, Sae Won

N1 - M1 - e0189848

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N2 - Background Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti–PD-1 antibody pembrolizumab was evaluated in 20 PD-L1–positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. Methods Patients with advanced, treatment-resistant PD-L1–positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate by investigator review per Response Evaluation Criteria in Solid Tumors version 1.1. Data cutoff was June 20, 2016. Results Of 137 patients with CRC and samples evaluable for PD-L1 expression, 33 (24%) had PD-L1–positive tumors, of which 23 were enrolled. Median follow-up was 5.3 months, and 8 patients (35%) reported treatment-related adverse events (AEs), most commonly fatigue (n = 3, 13%), stomatitis (n = 2, 9%), and asthenia (n = 2, 9%). One patient (4%) experienced grade 4 treatment-related increased blood bilirubin. No grade 3 AEs, discontinuations, or deaths were attributed to treatment. Most patients (n = 15, 65%) experienced progressive disease. One partial response occurred in a patient (4%) with MSI-high CRC. Conclusion Pembrolizumab demonstrated a favorable safety profile in advanced PD-L1–positive CRC. Antitumor activity was observed in a single patient with MSI-high CRC, warranting further evaluation in this patient population.

AB - Background Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti–PD-1 antibody pembrolizumab was evaluated in 20 PD-L1–positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. Methods Patients with advanced, treatment-resistant PD-L1–positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate by investigator review per Response Evaluation Criteria in Solid Tumors version 1.1. Data cutoff was June 20, 2016. Results Of 137 patients with CRC and samples evaluable for PD-L1 expression, 33 (24%) had PD-L1–positive tumors, of which 23 were enrolled. Median follow-up was 5.3 months, and 8 patients (35%) reported treatment-related adverse events (AEs), most commonly fatigue (n = 3, 13%), stomatitis (n = 2, 9%), and asthenia (n = 2, 9%). One patient (4%) experienced grade 4 treatment-related increased blood bilirubin. No grade 3 AEs, discontinuations, or deaths were attributed to treatment. Most patients (n = 15, 65%) experienced progressive disease. One partial response occurred in a patient (4%) with MSI-high CRC. Conclusion Pembrolizumab demonstrated a favorable safety profile in advanced PD-L1–positive CRC. Antitumor activity was observed in a single patient with MSI-high CRC, warranting further evaluation in this patient population.

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DO - 10.1371/journal.pone.0189848

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VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

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