Background: Anti-PD/PD-L1-targeted immunotherapy is associated with shockingly high rates of sustained clinical responses in patients with a variety of tumour types, despite the high prevalence of dermatological, gastrointestinal, and endocrine side effects. The hazards of pneumonitis and cardiotoxicity associated with checkpoint inhibitor therapy are understudied.A systematic analysis of the literature on randomised clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) methods was conducted in cancer patients. The rate of pneumonitis in IMM versus CTH was the primary outcome.Secondary endpoints included (I) high-grade pneumonitis rate in IMM compared to CTH, (II) tumour response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH, (III) cardiotoxicity grade comparison in IMM to others, (IV) cardiotoxicity grade difference between IMM and other studies with lung cancer and other cancer subgroups, and in IMM compared to chemotherapy (CTH) only studies, and (V) outcome of IMM We used a random model, a leave-one-out analysis, and meta-regression.Thirteen RCTs with a total of 7,246 patients for pneumonitis and 11 RCTs with a total of 6574 patients for cardiotoxicity were included in the study. When compared to the CTH arm, patients in the IMM arm had more high-grade and all-grade pneumonitis (OR =4.39, 95 percent CI =1.65–11.69, P=0.003 and OR =2.46, 95 percent CI =1.29–4.6, P=0.007). The immunotherapy arm had a significantly higher tumour response rate (OR =2.31, 95 percent CI =1.62–3.29, P0.001). Patients who received IMM had a longer PFS and OS than those who received CTH (HR =0.75, 95 percent CI =0.65–0.85, P0.001, and HR =0.71, 95 percent CI =0.66–0.77, P0.001). There was no difference in all-grade cardiotoxicity across all studies (RR: 1.15; 95 percent CI: 0.73–1.80; p = 0.55) or subgroups of lung cancer (RR: 0.68; 95 percent CI: 0.22–2.09; p = 0.50) or other malignancies (RR: 1.27; 95 percent CI: 0.78–2.08; p = 0.34). Similarly, there was no difference in high-grade cardiotoxicity across all trials (RR: 1.47; 95 percent CI: 0.87–2.46; p = 0.15) or across lung cancer subgroups (RR: 0.80; 95 percent CI: 0.25–2.50; p = 0.70) or other cancers (RR: 1.71, 95 percent CI: 0.96–3.06; p = 0.07).
Conclusions: Anti-PD-1 therapy produced more high-grade and all-grade pneumonitis than standard CTH regimens for NSCLC and melanoma, but not anti-PD-L1 therapy. Aside from that, the CTH arm had a higher rate of high-grade adverse events. IMM outperforms CTH in terms of tumour response rate, PFS, and overall survival. These findings can be used to assist patients choose the right therapy and set realistic treatment goals. Cardiotoxicity was statistically insignificant regardless of whether the patients received chemotherapy or dual immunotherapy. When utilised in the lung cancer subgroup, anti-PD/PDL1 produced improved response and survival rates.
Author(S) Details
Mohamed Rahouma
Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt and Cardiothoracic Surgery Departments, Weill Cornell Medicine, New York 14853, NY, USA.
Massimo Baudo
Cardiac Surgery Department, Spedali Civili di Brescia, Brescia, Italy.
Shon Shmushkevich
Cardiothoracic Surgery Departments, Weill Cornell Medicine, New York 14853, NY, USA and Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA.
Ayah Hassan
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Egypt.
Mostafa Rahouma
Information Technology Department, National Cancer Institute, Cairo University, Egypt.
Maha Yahia
Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Abdelrahman Mohamed
Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
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