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KUANetal.

TABLE XXV.9 (Continued)

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusions

Fanget al. 1711

Monotherapy trial: 1. 16% had grade 3 or 4 treatment-related AEs 2. 9% had treatment-related serious AE 3. ORR 34%, disease control in 59% with median follow-up 9.9 months 4. Median PFS 5.6 months Combination trial: 1. 87% had grade 3 or 4 treatment-related AEs 2. ORR 91%, disease control in 100%, median follow-up 10.2 months 3. Median PFS not reached, 6- and 12-month PFS 86% and 61%

1. Safety and tolerability 2. Preliminary antitumor activity (objective

93 patients with pretreated

2018 3

Two

single-arm, phase I trials

recurrent/metastatic NPC (23 treatment naïve patients) treated with camrelizumab monotherapy or combination therapy (camre lizumab + gemc itabine + cisplatin followed by

response/stable disease), PFS

camrelizumab maintenance)

Abbreviations: AE, adverse events; CPS, combined positive score; CRT, chemoradiation; DCR, disease control rate; DoR, duration of response; GC, gemc itabine + cisplatin; ITT, intention-to-treat; LN, lymph node; NPC, nasopharyngeal carcinoma; ORR, objective response rate; OS, overall survival; PD, disease progression; PF, cisplatin + 5-fluorouracil; PFS, progression-free survival; PR, partial response; RT, radiation therapy; TTR, time to response.

Combination of toripalimab 1713 or camrelizumab 1714 with GP in recurrent or metastatic NPC patients as first-line treatment provided improvement in median PFS, ORR, and duration of response, with no significant increase in grade 3–5 AEs. Treatment of metastatic NPC: Chemotherapy

locoregional RT improved 2-year OS and PFS, with no significant increase in acute hematological or gastroin testinal toxic effects. 1704 The finding was consistent with a meta-analysis comparing chemotherapy plus locoregional RT with chemotherapy alone in this group of patients, which also revealed improvement in ORR and DCR with locoregional RT. 1705 Immunotherapy with checkpoint inhibitors against PD 1 or PD-L1 offered promising pooled DCR of 63% and ORR of 27% in patients who are refractory to first line treatment in a meta-analysis. 1706 Phase II trials on monotherapy of camrelizumab (CAPTAIN study), 1707 nivolumab (NCI-9742), 1708 and toripalimab (POLARIS 02) 1709 on patients with refractory metastatic NPC revealed ORR of 28.2%, 20.5%, and 20.5% and DCR of 54.5%, 54.5%, and 40.0%, respectively. However, the phase III KEYNOTE-122 study 1710 on pembrolizumab failed to demonstrate a significant benefit compared with stan dard chemotherapy as second-line therapy. A phase I trial on camrelizumab monotherapy as second-line treatment revealed ORR of 34% and DCR of 59%. 1711 Meanwhile in the same study, combination of camrelizumab with GP in treatment-naïve patients provided an ORR of 91% and DCR of 100% with median follow-up time of 10.2 months. A pooled analysis comparing different immunotherapy regimens with chemotherapy alone showed that camre lizumab offered higher ORR, followed by pembrolizumab, as second- or later-line therapy. 1712 Two phase III trials on combination of immunotherapy with systemic chemother apy were conducted later to evaluate its efficacy and safety.

Aggregate grade of evidence

A (Level 1: three studies; Level 2: one study)

Benefit

Combination regimen of platinum-based chemotherapy improves OS and PFS in metastatic NPC. Increase in occurrence of grade 3–4 hematological toxicities. Combination regimen of platinum-based chemotherapy might increase the cost. Cost comparison analyses have not been undertaken. Preponderance of benefits over harms. Patients with metastatic NPC should be treated with combination regimen of platinum-based chemotherapy as first-line treatment.

Harm

Cost

Benefits–harm assessment

Value

judgments

Policy level Strong recommendation. Intervention Platinum-based combination chemotherapy,

preferably with gemcitabine, is the current first-line treatment for metastatic NPC.