Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma

Yannis Metaxas, Gareth Rivalland, Laetitia A. Mauti, Dirk Klingbiel, Steven Kao, Sabine Schmid, Anna K. Nowak, Oliver Gautschi, Tammo Bartnick, Brett G. Hughes, Hasna Bouchaab, Sacha I. Rothschild, Nick Pavlakis, Sibylle Wolleb, Ulf Petrausch, Kenneth O'Byrne, Patrizia Froesch, Melanie Löffler-Baumann, Susanne Pratsch-Peter, Prudence Russell & 7 others Walter Mingrone, Spasenija Savic, Bibhusal Thapa, Martin Früh, Miklos Pless, Roger von Moos, Thomas John

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Abstract

Introduction: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). Methods: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%). Results: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. Conclusion: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.

Original languageEnglish
Pages (from-to)1784-1791
Number of pages8
JournalJournal of Thoracic Oncology
Volume13
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018

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Immunotherapy
Ligands
Disease-Free Survival
Switzerland
Therapeutics
Survival
pembrolizumab
Malignant Mesothelioma
Registries
Survival Rate

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Metaxas, Y., Rivalland, G., Mauti, L. A., Klingbiel, D., Kao, S., Schmid, S., ... John, T. (2018). Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma. Journal of Thoracic Oncology, 13(11), 1784-1791. https://doi.org/10.1016/j.jtho.2018.08.007
Metaxas, Yannis ; Rivalland, Gareth ; Mauti, Laetitia A. ; Klingbiel, Dirk ; Kao, Steven ; Schmid, Sabine ; Nowak, Anna K. ; Gautschi, Oliver ; Bartnick, Tammo ; Hughes, Brett G. ; Bouchaab, Hasna ; Rothschild, Sacha I. ; Pavlakis, Nick ; Wolleb, Sibylle ; Petrausch, Ulf ; O'Byrne, Kenneth ; Froesch, Patrizia ; Löffler-Baumann, Melanie ; Pratsch-Peter, Susanne ; Russell, Prudence ; Mingrone, Walter ; Savic, Spasenija ; Thapa, Bibhusal ; Früh, Martin ; Pless, Miklos ; von Moos, Roger ; John, Thomas. / Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma. In: Journal of Thoracic Oncology. 2018 ; Vol. 13, No. 11. pp. 1784-1791.
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abstract = "Introduction: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). Methods: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5{\%}), intermediate (5{\%}-49{\%}), and high (≥50{\%}). Results: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73{\%}) had epithelioid MPM, and 67 (72{\%}) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52{\%}). PD-L1 expression results were available for 66 patients (71{\%}). Most (68{\%}) were negative, 18{\%} were intermediate, and 14{\%} were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18{\%}, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37{\%}, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24{\%} versus 16{\%} [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44{\%} versus 42{\%} versus 11{\%} [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. Conclusion: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.",
keywords = "Immunotherapy, Mesothelioma, PD-1, Pembrolizumab, Second-line therapy",
author = "Yannis Metaxas and Gareth Rivalland and Mauti, {Laetitia A.} and Dirk Klingbiel and Steven Kao and Sabine Schmid and Nowak, {Anna K.} and Oliver Gautschi and Tammo Bartnick and Hughes, {Brett G.} and Hasna Bouchaab and Rothschild, {Sacha I.} and Nick Pavlakis and Sibylle Wolleb and Ulf Petrausch and Kenneth O'Byrne and Patrizia Froesch and Melanie L{\"o}ffler-Baumann and Susanne Pratsch-Peter and Prudence Russell and Walter Mingrone and Spasenija Savic and Bibhusal Thapa and Martin Fr{\"u}h and Miklos Pless and {von Moos}, Roger and Thomas John",
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Metaxas, Y, Rivalland, G, Mauti, LA, Klingbiel, D, Kao, S, Schmid, S, Nowak, AK, Gautschi, O, Bartnick, T, Hughes, BG, Bouchaab, H, Rothschild, SI, Pavlakis, N, Wolleb, S, Petrausch, U, O'Byrne, K, Froesch, P, Löffler-Baumann, M, Pratsch-Peter, S, Russell, P, Mingrone, W, Savic, S, Thapa, B, Früh, M, Pless, M, von Moos, R & John, T 2018, 'Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma' Journal of Thoracic Oncology, vol. 13, no. 11, pp. 1784-1791. https://doi.org/10.1016/j.jtho.2018.08.007

Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma. / Metaxas, Yannis; Rivalland, Gareth; Mauti, Laetitia A.; Klingbiel, Dirk; Kao, Steven; Schmid, Sabine; Nowak, Anna K.; Gautschi, Oliver; Bartnick, Tammo; Hughes, Brett G.; Bouchaab, Hasna; Rothschild, Sacha I.; Pavlakis, Nick; Wolleb, Sibylle; Petrausch, Ulf; O'Byrne, Kenneth; Froesch, Patrizia; Löffler-Baumann, Melanie; Pratsch-Peter, Susanne; Russell, Prudence; Mingrone, Walter; Savic, Spasenija; Thapa, Bibhusal; Früh, Martin; Pless, Miklos; von Moos, Roger; John, Thomas.

In: Journal of Thoracic Oncology, Vol. 13, No. 11, 01.11.2018, p. 1784-1791.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma

AU - Metaxas, Yannis

AU - Rivalland, Gareth

AU - Mauti, Laetitia A.

AU - Klingbiel, Dirk

AU - Kao, Steven

AU - Schmid, Sabine

AU - Nowak, Anna K.

AU - Gautschi, Oliver

AU - Bartnick, Tammo

AU - Hughes, Brett G.

AU - Bouchaab, Hasna

AU - Rothschild, Sacha I.

AU - Pavlakis, Nick

AU - Wolleb, Sibylle

AU - Petrausch, Ulf

AU - O'Byrne, Kenneth

AU - Froesch, Patrizia

AU - Löffler-Baumann, Melanie

AU - Pratsch-Peter, Susanne

AU - Russell, Prudence

AU - Mingrone, Walter

AU - Savic, Spasenija

AU - Thapa, Bibhusal

AU - Früh, Martin

AU - Pless, Miklos

AU - von Moos, Roger

AU - John, Thomas

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Introduction: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). Methods: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%). Results: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. Conclusion: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.

AB - Introduction: There is no approved second-line treatment for malignant pleural mesothelioma (MPM). On the basis of promising early results, pembrolizumab was used off-label in Switzerland and Australia. We investigated outcomes in association with clinicopathological features and expression of programmed death ligand 1 (PD-L1). Methods: Registry data in Australia and Switzerland were pooled. Patient characteristics, including age, sex, histological subtype, and previous treatments were captured. Outcomes were assessed locally. PD-L1 expression was categorized as negative (<5%), intermediate (5%-49%), and high (≥50%). Results: A total of 93 patients (48 from Switzerland and 45 from Australia) were treated; 68 patients (73%) had epithelioid MPM, and 67 (72%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. Pembrolizumab was the second-line treatment in 48 of 93 patients (52%). PD-L1 expression results were available for 66 patients (71%). Most (68%) were negative, 18% were intermediate, and 14% were high for PD-L1 expression. In the full cohort, the overall response rate (ORR) was 18%, the median progression-free survival (mPFS) was 3.1 months, and the median overall survival was 7.2 months. In patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 and only one previous systemic treatment (n = 35), the ORR was 37%, the mPFS was 3.7 months, and the median overall survival was 10.2 months. The nonepitheloid histological subtype showed an improved ORR (24% versus 16% [p = 0.54) and mPFS (5.6 versus 2.8 months [p = 0.02]). Compared with intermediate and negative PD-L1 expression, high PD-L1 expression was associated with an improved ORR (44% versus 42% versus 11% [p = 0.01]) and mPFS (6.2 versus 3.9 versus 2.7 months [p = 0.04]). Toxicity was as expected. Conclusion: These real-world data demonstrate similar response rates but inferior survival compared with those in early-phase trials. High PD-L1 expression and nonepitheloid histological subtype were associated with greater activity. Anti–PD-L1 immunotherapy is a reasonable second-line therapy in patients with MPM.

KW - Immunotherapy

KW - Mesothelioma

KW - PD-1

KW - Pembrolizumab

KW - Second-line therapy

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U2 - 10.1016/j.jtho.2018.08.007

DO - 10.1016/j.jtho.2018.08.007

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EP - 1791

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

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Metaxas Y, Rivalland G, Mauti LA, Klingbiel D, Kao S, Schmid S et al. Pembrolizumab as Palliative Immunotherapy in Malignant Pleural Mesothelioma. Journal of Thoracic Oncology. 2018 Nov 1;13(11):1784-1791. https://doi.org/10.1016/j.jtho.2018.08.007