Adjuvant cisplatin-gemcitabine ups PFS vs cisplatin-fluorouracil in N2–3 NPC after cCRT

In Chinese patients with stage N2–3 nasopharyngeal carcinoma (NPC) who have completed concurrent chemoradiotherapy (cCRT), adjuvant cisplatin-gemcitabine significantly improves progression-free survival (PFS) vs current standard of care (SoC) with adjuvant cisplatin-fluorouracil, according to a phase III trial at four cancer centres in China that was reported at ASCO 2023.

The open-label, parallel-group, randomized controlled trial included 240 patients aged 18–65 years (median age, 44 years; male, 73 percent) with nonkeratinizing T1–4 N2–3 M0 NPC, an Eastern Cooperative Oncology Group performance status of 0–1, and adequate bone marrow, liver and renal function. The patients were randomized 1:1 to receive adjuvant cisplatin (80 mg/m² intravenously [IV] for 4 hours on day 1) and gemcitabine (1 g/m² IV on days 1 and 8) Q3W (n=120) or adjuvant cisplatin and fluorouracil (4 g/m² in continuous IV infusion for 96 hours) Q4W (n=120), for up to 3 cycles, following cCRT with cisplatin (100 mg/m² IV) administered on days 1, 22 and 43 of intensity-modulated radiotherapy. Randomization was stratified by treatment centre and nodal category. Adjuvant cisplatin-gemcitabine and cisplatin-fluorouracil were started at a median of 35 days and 34 days from the last day of radiotherapy, respectively. [Tang LQ, ASCO 2023, abstract 6000; Lancet Oncol 2023;doi:10.1016/S1470-2045(23)00232-2]
After a median follow-up of 40 months, the primary endpoint of 3-year PFS rate was 83.9 percent in the cisplatin-gemcitabine group vs 71.5 percent in the cisplatin-fluorouracil group (stratified hazard ratio [HR], 0.54; 95 percent confidence interval [CI], 0.32–0.93; log rank p=0.023).

At 3 years, the cumulative incidence of locoregional relapse was 2.6 percent vs 13.2 percent in the cisplatin-gemcitabine vs cisplatin-fluorouracil group (HR, 0.33; 95 percent CI, 0.12–0.90; Fine-Gray p=0.030), while the cumulative incidence of distant metastasis was 10.9 percent vs 22.3 percent (HR, 0.50; 95 percent CI, 0.26–0.98; Fine-Gray p=0.042).

Three-year overall survival rate was 90.7 percent in the cisplatin-gemcitabine group vs 94.0 percent in the cisplatin-fluorouracil group (HR, 1.17; 95 percent CI, 0.51–2.66; log-rank p=0.71).

“In multivariable analyses, patients in the cisplatin-gemcitabine group had reduced risks of disease progression or death, locoregional relapse, and distant metastasis compared with those in the cisplatin-fluorouracil group,” the investigators noted.

The most common grade ≥3 acute adverse events (AEs) were leucopenia (52 percent vs 29 percent with cisplatin-gemcitabine vs cisplatin-fluorouracil; p=0.00039), neutropenia (32 percent vs 16 percent; p=0.010), and mucositis (23 percent vs 28 percent; p=0.43). The most common grade ≥3 late AEs that occurred from 3 months after completion of radiotherapy was auditory or hearing loss (5 percent vs 9 percent).

Dose reductions were reported in 17 percent vs 21 percent of patients in the cisplatin-gemcitabine vs cisplatin-fluorouracil group during the concurrent phase, and in 53 percent vs 40 percent of patients during the adjuvant phase. Treatment discontinuation occurred in 45 percent vs 40 percent of patients. The most common AEs leading to treatment discontinuation were leucopenia (7 percent) and thrombocytopenia (3 percent) in the cisplatin-gemcitabine group, and leucopenia (3 percent) and anaemia (2 percent) in the cisplatin-fluorouracil group.

One patient (1 percent) in the cisplatin-gemcitabine died due to treatment-related complication (septic shock caused by neutropenic infection).

“These findings support the potential role of adjuvant cisplatin-gemcitabine as a treatment option for patients with locoregionally advanced NPC,” the researchers concluded. “Further studies are needed in more globally diverse populations to confirm these findings and determine the optimal therapeutic dose. Haematological toxicity of the cisplatin-gemcitabine regimen should be carefully managed during treatment.”