Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials

Abstract

Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1–5 AEs whereas camrelizumab and nivolumab regarding grade 3–5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1–positive and PD-L1–negative patients, respectively ( P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

“…26 This review differs from previous articles by providing a comprehensive analysis of both current and future immunotherapy NPC trials. 18,29…”

“…Subtype III, with high expression of T effector genes and high IFNγ signature, may be enriched for potential responders to checkpoint blockade therapy . This review differs from previous articles by providing a comprehensive analysis of both current and future immunotherapy NPC trials …”

Looking for the Optimal PD-1/PD-L1 Inhibitor in Cancer Treatment: A Comparison in Basic Structure, Function, and Clinical Practice

“…The results showed that the ORRs of nivolumab-treated patients in PD-L1-positive and -negative subgroups were 39.3% (34.1-44.4%) and 22.9% (19.4-26.3%), respectively, while the corresponding rates in pembrolizumabtreated patients were 30.3% (25.2-35.3%) and 10.8% (3.3-18.4%), respectively (90). Moreover, in a pooled analysis of secondor later-line treatment of nasopharyngeal cancer, camrelizumab (34.1%) exhibited the highest ORR, followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%) (91). Besides, Duan J et al conducted a meta-analysis with an adjusted mirror principal to explore the potential differences in PD-1/PD-L1 inhibitors.…”

“…Moreover, a pooled analysis of nasopharyngeal cancer patients showed that the incidence rates of grade 1-5/3-5 AEs are 74.1/29.6, 54.2/17.4, 92.3/24.5, and 96.8/16.1% for pembrolizumab, nivolumab, JS001, and camrelizumab, respectively. This further indicates that, with respect to grade 1-5 AEs, nivolumab and pembrolizumab may be superior options, but when considering grade 3-5 AEs, camrelizumab and nivolumab show more favorable safety (91).…”

“…Immune-related AEs have been observed for nearly all of the PD-1/PD-L1 inhibitors ( Table 3). They include fatigue, decreased appetite, diarrhea, hypothyroidism, hyperthyroidism, pneumonitis, skin reactions, and colitis (91,94). In addition to excessive immune activation, another important cause of antibody-induced AEs is off-target binding.…”