TY - JOUR
T1 - Pneumonitis as a complication of immune system targeting drugs?—a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials
AU - Rahouma, Mohamed
AU - Baudo, Massimo
AU - Yahia, Maha
AU - Kamel, Mohamed
AU - Gray, Katherine D.
AU - Elmously, Adham
AU - Ghaly, Galal
AU - Eldessouki, Ihab
AU - Abouarab, Ahmed
AU - Cheriat, Ali N.
AU - Karim, Naglaa Abdel
AU - Mohamed, Abdelrahman
AU - Morris, John
AU - Gaudino, Mario
N1 - Publisher Copyright:
© Journal of Thoracic Disease. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Background: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. Methods: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. Results: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65–11.69, P=0.003 and OR =2.46, 95% CI: 1.29–4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62–3.29, P<0.001). PFS and OS were longer in patients who received IMM compared to patients in the CTH arm (HR =0.75, 95% CI: 0.65–0.85, P<0.001, and HR =0.71, 95% CI: 0.66–0.77, P<0.001). Conclusions: The incidence of high-grade and all-grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma. High-grade adverse events were otherwise more common in the CTH arm. Tumor response rate, PFS, and OS are all substantially improved with IMM over CTH. These results can be used to guide therapy selection and set expectations for treatment effect in these patients.
AB - Background: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. Methods: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. Results: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65–11.69, P=0.003 and OR =2.46, 95% CI: 1.29–4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62–3.29, P<0.001). PFS and OS were longer in patients who received IMM compared to patients in the CTH arm (HR =0.75, 95% CI: 0.65–0.85, P<0.001, and HR =0.71, 95% CI: 0.66–0.77, P<0.001). Conclusions: The incidence of high-grade and all-grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma. High-grade adverse events were otherwise more common in the CTH arm. Tumor response rate, PFS, and OS are all substantially improved with IMM over CTH. These results can be used to guide therapy selection and set expectations for treatment effect in these patients.
KW - Immunotherapy
KW - Pembrolizumab
KW - Pneumonitis
KW - Response
KW - Survival
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U2 - 10.21037/jtd.2019.01.19
DO - 10.21037/jtd.2019.01.19
M3 - Article
AN - SCOPUS:85065982730
SN - 2072-1439
VL - 11
SP - 521
EP - 534
JO - Journal of Thoracic Disease
JF - Journal of Thoracic Disease
IS - 2
ER -