Paclitaxel induction chemotherapy regimen more effective in nasopharyngeal carcinoma
Induction chemotherapy with paclitaxel, cisplatin and capecitabine vs. cisplatin and fluorouracil improved failure-free survival among patients with advanced nasopharyngeal carcinoma, according to a study published in JAMA Oncology.
Results of the randomized, open-label, phase 3 trial also showed the paclitaxel combination did not result in a higher rate of serious adverse events, researchers noted.
Rationale and methods
The addition of induction chemotherapy to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma; however, the optimal induction regimen remains unclear, according to Wang-Zhong Li, MD, researcher in the department of nasopharyngeal carcinoma at Sun Yat-sen University Cancer Center in China, and colleagues wrote.
Li and colleagues compared two regimens among 238 patients (median age, 45 years; 78.6% men) with treatment-naive, nonkeratinizing stage IVA to stage IVB nasopharyngeal carcinoma and an ECOG status of 0 to 1 across four hospitals in China between Oct. 20, 2016, and Aug. 29, 2019.
The researchers assigned patients to induction chemotherapy with either two, 21-day cycles of 150 mg/m² paclitaxel on day 1, 60 mg/m² cisplatin on day 1 and 1,000 mg/m² oral twice-daily capecitabine on days 1 to 14 (n = 118) or 100 mg/m²cisplatin on day 1 and 800 mg/m² fluorouracil on days 1 to 5 before chemoradiotherapy (n = 120).
Failure-free survival among the intention-to-treat cohort served as the primary endpoint. Secondary endpoints included distant metastasis-free survival, locoregional relapse-free survival, OS, tumor response and safety.
Median follow-up was 48.4 months.
Key findings
Results showed a 3-year failure-free survival rate of 83.5% (95% CI, 77-90.6) among those assigned induction chemotherapy with paclitaxel, cisplatin and capecitabine compared with 68.9% (95% CI, 61.1-77.8) with cisplatin and fluorouracil (stratified HR for recurrence or death = 0.47; 95% CI, 0.28-0.79).
In addition, patients assigned the induction chemotherapy regimen experienced a significant reduction in risk for distant metastases (stratified HR = 0.49; 95% CI, 0.24-0.98) and locoregional recurrence (stratified HR = 0.4; 95% CI, 0.18-0.93). Conversely, researchers observed no difference in the effect of the induction chemotherapy regimen on early OS (stratified HR = 0.45; 95% CI, 0.17-1.18).
Overall, 57.6% of patients assigned the paclitaxel regimen vs. 65.8% of patients assigned cisplatin and fluorouracil experienced grade 3 to grade 4 acute adverse events, and 13.6% vs. 17.9% experienced late-onset toxicities. Researchers observed one treatment-associated death, in the cisplatin and fluorouracil group.
The researchers reported several study limitations, including that patients came from endemic areas in China where nonkeratinizing nasopharyngeal carcinoma constitutes more than 95% of cases; thus, the findings may not be generalizable to nonendemic regions. In addition, researchers did not include children, adolescents and older adults, and although the trial met its primary endpoint of failure-free survival, early OS results did not achieve statistical significant.
“Longer follow-up is needed to confirm whether there is a benefit of OS,” Li and colleagues wrote.
Implications
Both adjuvant and induction chemotherapy improve outcomes in patients with advanced nasopharyngeal carcinoma when sequenced with concurrent chemoradiotherapy, but the dilemma is in validating the superiority of one sequence over the other, according to an accompanying editorial by Maurice Willis, MD, professor in the department of general oncology at The University of Texas MD Anderson Cancer Center and The University of Texas Medical Branch.
“Although one needs to exercise caution extrapolating these results clinically until more enduring mature results are available, this trial addresses an unmet need and brings paclitaxel, cisplatin and capecitabine into the armamentarium for induction therapies in advanced nasopharyngeal carcinoma,” Willis wrote.
References:
- Li WZ, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.0122.
- Willis M, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2022.0082.
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