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
UR - http://www.scopus.com/inward/record.url?scp=85055255453&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2018.08.007
DO - 10.1016/j.jtho.2018.08.007
M3 - Article
C2 - 30142389
AN - SCOPUS:85055255453
SN - 1556-0864
VL - 13
SP - 1784
EP - 1791
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 11
ER -