Addition of radiotherapy to chemotherapy extends OS in metastatic nasopharyngeal carcinoma
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Radiotherapy in combination with chemotherapy significantly improved OS among chemotherapy-sensitive patients with metastatic nasopharyngeal carcinoma, according to results of a randomized phase 3 study published in JAMA Oncology.
“Incidences of synchronous distant metastasis in endemic nasopharyngeal carcinoma (NPC) range from 6% to 8% at the time of presentation,” Rui You, MD, clinical researcher in the department of nasopharyngeal carcinoma at Sun Yat-sen University Cancer Center in China, and colleagues wrote. “In these patients, gemcitabine and cisplatin doublet chemotherapy is the standard of care as first-line treatment.”
Median OS for patients with de novo metastatic NPC treated with gemcitabine and cisplatin is 29.1 months. However, previous studies have shown that local therapy can be used for metastatic disease to reduce primary tumor burden, relieve symptoms or treat metastases. Other studies have suggested that it can prolong OS.
You and colleagues evaluated the safety and efficacy of locoregional radiotherapy among 126 patients (median age, 46 years; interquartile range [IQR], 39-52; 83.3% men) with biopsy-proven metastatic NPC. All patients demonstrated complete or partial response after three cycles of cisplatin and fluorouracil chemotherapy.
Researchers randomly assigned study participants to chemotherapy in combination with radiotherapy (n = 63) or chemotherapy alone (n = 63). Chemotherapy regimens consisted of 5 g/m2 fluorouracil administered via continuous IV infusion over 120 hours and 100 mg/m2 IV cisplatin on day 1 every 3 weeks for six cycles.
Patients assigned to the combination group received intensity-modulated radiotherapy following chemotherapy.
OS served as the primary endpoint. PFS and safety served as secondary endpoints.
Median follow-up was 26.7 months (IQR, 17.2-33.5)
Results showed 24-month OS of 76.4% (95% CI, 64.4-88.4) in the combination group compared with 54.5% (95% CI, 41-68) in the chemotherapy-alone group; thus, the study met its primary endpoint of improved OS (stratified HR = 0.42; 95% CI, 0.23-0.77) with the combination treatment.
The combination also conferred longer PFS compared with chemotherapy alone (stratified HR = 0.36; 95% CI, 0.23-0.57).
Researchers observed no significant differences in acute hematological or gastrointestinal toxic effects between the two groups. Grade 3 or higher acute adverse events specific to radiotherapy in the combination group included mucositis (33.9%), dermatitis (8.1%) and xerostomia (6.5%). Late grade 3 or higher toxic effects specific to radiotherapy included hearing loss (5.2%) and trismus (3.4%).
“To our knowledge, this is the first randomized phase 3 clinical trial evaluating the efficacy of definitive locoregional IMRT when added to the backbone of palliative chemotherapy in patients with de novo metastatic NPC,” You and colleagues wrote. “These findings suggest that chemotherapy plus high-dose locoregional radiotherapy improves survival in [these] chemotherapy-sensitive patients.”
Although the data should influence the standard of care, “a number of questions remain as to what is the optimal systemic therapy to move forward with these findings into current clinical practice,” Nadeem Riaz, MD, MSc, radiation oncologist in the department of radiation oncology at Memorial Sloan Kettering Cancer Center, and colleagues wrote in a related editorial.
“What remains to be determined is the role of radiotherapy to metastatic foci and how to integrate these findings with the evolving landscape of front-line systemic therapy for metastatic NPC,” Riaz and colleagues wrote.
References
- Riaz N, et al. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.1793.
- You R, et al. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.1808.
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