Chemotherapy/Immunotherapy

The international, multicenter, randomized, double-blind, phase III JUPITOR-02 study (NCT03581786) was conducted in nasopharyngeal carcinoma–endemic regions, including mainland China, Taiwan, and Singapore. The trial randomly assigned 289 patients to receive either toripalimab, a humanized IgG4K monoclonal antibody against human programmed death 1 (PD-1), (240 mg/m2) or placebo in combination with gemcitabine and cisplatin for up to six cycles. Patients also received maintenance therapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. The primary end point was progression-free survival (PFS) as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival (OS), PFS as assessed by an investigator, duration of response, and safety. The median survival follow-up was 36 months.[21]

The international, multicenter, randomized, double-blind, phase III JUPITOR-02 study (NCT03581786) was conducted in nasopharyngeal carcinoma–endemic regions, including mainland China, Taiwan, and Singapore. The trial randomly assigned 289 patients to receive either toripalimab, a humanized IgG4K monoclonal antibody against human programmed death 1 (PD-1), (240 mg/m2) or placebo in combination with gemcitabine and cisplatin for up to six cycles. Patients also received maintenance therapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. The primary end point was progression-free survival (PFS) as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival (OS), PFS as assessed by an investigator, duration of response, and safety. The median survival follow-up was 36 months.[21]

The median OS was not reached in the toripalimab group (95% confidence interval [CI], 38.7 months–not estimable) and was 33.7 months (95% CI, 27.0–44.2) in the placebo group (hazard ratio [HR], 0.63; 95% CI, 0.45–0.89; P = .0083).[21][Level of evidence A1]

The international, multicenter, randomized, double-blind, phase III JUPITOR-02 study (NCT03581786) was conducted in nasopharyngeal carcinoma–endemic regions, including mainland China, Taiwan, and Singapore. The trial randomly assigned 289 patients to receive either toripalimab, a humanized IgG4K monoclonal antibody against human programmed death 1 (PD-1), (240 mg/m2) or placebo in combination with gemcitabine and cisplatin for up to six cycles. Patients also received maintenance therapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. The primary end point was progression-free survival (PFS) as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival (OS), PFS as assessed by an investigator, duration of response, and safety. The median survival follow-up was 36 months.[21]

PFS was significantly longer in the toripalimab arm compared with the placebo arm, with a median PFS of 21.4 months in the toripalimab group versus 8.2 months in the placebo group (HR, 0.52; 95% CI, 0.37–0.73).

The international, multicenter, randomized, double-blind, phase III JUPITOR-02 study (NCT03581786) was conducted in nasopharyngeal carcinoma–endemic regions, including mainland China, Taiwan, and Singapore. The trial randomly assigned 289 patients to receive either toripalimab, a humanized IgG4K monoclonal antibody against human programmed death 1 (PD-1), (240 mg/m2) or placebo in combination with gemcitabine and cisplatin for up to six cycles. Patients also received maintenance therapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. The primary end point was progression-free survival (PFS) as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival (OS), PFS as assessed by an investigator, duration of response, and safety. The median survival follow-up was 36 months.[21]

Grade 3 or higher immune-related adverse events occurred in 9.6% of patients in the toripalimab group. Treatment discontinuation occurred in 11.6% of patients in the toripalimab group and 4.9% of patients in the placebo group.

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

The median follow-up time for PFS was 19.4 months (interquartile range [IQR], 12.1–35.6). The median PFS was 7.0 months (range, 4.4–10.9) in the gemcitabine group and 5.6 months (range, 3.0–7.0) in the 5-FU group (HR, 0.55; 95% CI, 0.44–0.68; P < .0001).[22][Level of evidence B1]

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

There were significant differences in the incidences of the following grade 3 or 4 treatment-related adverse events:

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group. › There were significant differences in the incidences of the following grade 3 or 4 treatment-related adverse events:

Leukopenia (52 [29%] in the gemcitabine group vs.15 [9%] in the 5-FU group; P < .0001).

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group. › There were significant differences in the incidences of the following grade 3 or 4 treatment-related adverse events:

Neutropenia (41 [23%] in the gemcitabine group vs. 23 [13%] in the 5-FU group; P = .0251).

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group. › There were significant differences in the incidences of the following grade 3 or 4 treatment-related adverse events:

Thrombocytopenia (24 [13%] in the gemcitabine group vs. 3 [2%] in the 5-FU group; P = .0007).

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group. › There were significant differences in the incidences of the following grade 3 or 4 treatment-related adverse events:

Mucosal inflammation (0 in the gemcitabine group vs. 25 [14%] in the 5-FU group; P < .0001).

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

Serious treatment-related adverse events occurred in seven patients (4%) in the gemcitabine group and ten patients (6%) in the 5-FU group.

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

Six patients (3%) in the gemcitabine group and 14 patients (8%) in the 5-FU group discontinued treatment because of drug-related adverse events.

A multicenter, randomized, open-label, phase III trial included patients with recurrent or metastatic nasopharyngeal carcinoma recruited from 22 hospitals in China. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously [IV] on days 1 and 8) and cisplatin (80 mg/m2 IV on day 1), or fluorouracil ([5-FU] 4 g/m2 in continuous IV infusion over 96 h) and cisplatin (80 mg/m2 IV on day 1) once every 3 weeks for a maximum of six cycles.[22] Of the 362 patients, 181 were assigned to the gemcitabine-plus-cisplatin group and 181 to the 5-FU-plus-cisplatin group.

No treatment-related deaths occurred in either group.

POLARIS-02 (NCT02915432) was a phase II, open-label, multicenter, single-arm trial in China that enrolled 190 patients with recurrent or metastatic nasopharyngeal carcinoma. Patients received toripalimab (3 mg/kg) once every 2 weeks until disease progression or unacceptable toxicity. Patients had received prior platinum-based chemotherapy or had disease progression within 6 months of completion of platinum-based chemotherapy given as neoadjuvant, adjuvant, or definitive chemoradiation therapy for locally advanced disease. The primary end point was objective response rate. The secondary end points included safety, duration of response, PFS, and OS.[23]

POLARIS-02 (NCT02915432) was a phase II, open-label, multicenter, single-arm trial in China that enrolled 190 patients with recurrent or metastatic nasopharyngeal carcinoma. Patients received toripalimab (3 mg/kg) once every 2 weeks until disease progression or unacceptable toxicity. Patients had received prior platinum-based chemotherapy or had disease progression within 6 months of completion of platinum-based chemotherapy given as neoadjuvant, adjuvant, or definitive chemoradiation therapy for locally advanced disease. The primary end point was objective response rate. The secondary end points included safety, duration of response, PFS, and OS.[23]

The objective response rate was 20.5%, with a median duration of response of 12.8 months, a median PFS of 1.9 months, and a median OS of 17.4 months.[23][Level of evidence C3]