Locoregional Radiation Extends Metastatic Nasopharyngeal Cancer OS

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: Use of locoregional radiotherapy significantly improved overall survival (OS) for patients with chemosensitive metastatic nasopharyngeal carcinoma (mNPC) participating in a phase III clinical trial.

Finding no significant differences in acute haematological or gastrointestinal toxicities between the patients given chemotherapy with or without radiotherapy, the researchers write in JAMA Oncology that “[c]ollectively, these results support a new [standard of care] for chemotherapy-sensitive de novo mNPC.”

The study participants had all previously achieved at least a partial response to three cycles of fluorouracil and cisplatin chemotherapy before being randomly assigned to continue with another six cycles alone or followed by intensity-modulated radiotherapy beginning 21 days after chemotherapy was completed.

Radiation was administered in 33 fractions, 5 days/week, and included target volumes of 70 Gy to the primary tumour and retropharyngeal nodes and 60–66 Gy to the gross cervical lymph nodes, explain Ming-Yuan Chen, from Sun Yat-sen University Cancer Center in Guangzhou, China, and co-authors.

After a median 26.7 months of follow-up, 24-month OS was achieved by 76.4% of the 63 patients assigned to receive chemoradiation and 54.5% of the 63 given chemotherapy alone, giving a significant stratified hazard ratio for death of 0.42 that favoured the combination strategy.

Patients given chemoradiation also had significantly better progression-free survival than those given only chemotherapy, at a median 12.4 versus 6.7 months and a stratified hazard ratio of 0.36.

The objective response rate at the end of the six chemotherapy cycles was a comparable 80.9% and 82.5% for the chemoradiation and chemotherapy groups, respectively. For patients given radiation, the objective response rate at the end of treatment was 75.4% and there was a rise in complete responses from 7.9% to 16.4%. Two patients were not assessable after radiation.

Second-line chemotherapy at the time of progression was given to 57.1% of patients treated with chemoradiation after a median 11.8 months versus 65.1% of chemotherapy-only patients after a median 7.7 months.

Safety analysis indicated that neutropenia was the most common grade 3–4 adverse event, affecting 56.5% and 54.7% of the chemoradiation and chemotherapy only groups, respectively. Radiation was associated with acute grade 3 or worse mucositis (33.9%), dermatitis (8.1%) and xerostomia (6.5%), as well as late-onset hearing loss (5.2%) and trismus (3.4%) at this severity.

The researchers suggest that the “high tolerance to cisplatin” in the study might be “owing to strict hydration and the use of furosemide and mannitol” to avoid renal toxicity, as well as adherence to protocol-defined drug dose adjustments to reduce gastrointestinal and renal toxicity.

Noting that locoregional radiation was associated with a reduced risk of regional relapse (3.2 vs 9.5%) and distant metastatic recurrence relative to chemotherapy alone (54.0 vs 68.3%), the researchers hypothesise “that targeting the index tumor lesion could delay the seeding of subsequent tumor clones at distant sites.”

The authors of a linked commentary observe that around third of patients in the study had one or two metastatic sites and had better OS than those with three or more metastatic sites in subgroup analysis of the treatment groups (HR=0.15 and 0.45, respectively, favouring chemoradiation in both groups).

“Whether consolidative radiotherapy to metastatic sites for these patients and for those with even larger numbers of metastatic lesions would have led to further increase in durable long-term control warrants additional study”, write Nancy Lee, from Memorial Sloan-Kettering Cancer Center in New York, USA, and colleagues.

But they caution that “[t]reatment to increased sites of metastatic disease would clearly need to be balanced against known toxic effects from irradiating oligometastatic sites.”

References

• You R, Liu Y-P, Huang P-Y, et al. Efficacy and safety of locoregional radiotherapy with chemotherapy vs chemotherapy alone in de novo metastatic nasopharyngeal carcinoma. A multicenter phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 23 July 2020. doi:10.1001/jamaoncol.2020.1808
• Riaz N, Sherman E, Lee N. The importance of locoregional therapy in metastatic nasopharyngeal cancer. JAMA Oncol; Advance online publication 23 July 2020. doi:10.1001/jamaoncol.2020.1793