A New Standard of Care for Stage 4 Nasopharyngeal Cancer: Consolidation Radiotherapy

The nasopharynx is the upper part of the pharynx, located behind the nose. Cancers arising in this region are classified among head and neck cancers, and nasopharyngeal cancer is common worldwide, particularly among men in Southeast Asia (22 - 27 new cases annually per 100 thousand people).

At diagnosis, around 6-8% of nasopharyngeal cancers are metastatic (stage 4). The standard treatment for these patients is systemic chemotherapy (the cisplatin + gemcitabine combination regimen). With this initial treatment, median overall survival in patients with stage 4 nasopharyngeal cancer is reported to be 29.1 months. However, various retrospective (past observational) studies have suggested that adding radiotherapy, a regional treatment, to these systemic chemotherapies contributes around 17-20% to overall survival. In other words, in metastatic cancer, systemic treatment plus radiotherapy to the primary tumor site appears to improve overall treatment outcomes. Until now, however, there has been no phase-III prospective (forward-looking) clinical trial supporting this favorable observation. 

The results of the first multicenter, randomized, open-ended, double-blind prospective phase III clinical trial conducted for this purpose were published on July 23, 2020 in JAMA Oncology.

The study enrolled 126 patients with metastatic nasopharyngeal cancer at diagnosis and compared the effectiveness of regional radiotherapy with concurrent chemotherapy against standard chemotherapy.

Study details

• Patients were enrolled between April 2014 - August 2018.
• The median follow-up period was 26.7 months.
• Study inclusion criteria:
  • Being aged 18-65,
  • Having a radiological partial or complete response after 3 cycles of the cisplatin plus 5FU combination chemotherapy regimen,
  • Not having previously received systemic treatment and/or radiotherapy for nasopharyngeal cancer,
  • Having a good overall performance score (KPS>70).

The study included 126 patients who met the criteria above;

• 63 patients were assigned to standard treatment with 6 cycles of cisplatin plus 5FU,
• 63 patients were assigned to cisplatin plus 5FU and concurrent intensity-modulated radiotherapy (the IMRT technique).

Study results

• There was no significant difference between the two groups in treatment-related adverse events.
• At 24 months, the overall survival rate was 76.4% (64.4 - 88.4) in the chemoradiotherapy arm and 54.5% (41 - 68) in the chemotherapy-only arm, HR:0.42.
• Median progression-free survival was 12.4 months (10.5 - 14.2) in the chemoradiotherapy arm and 6.7 months (5.4 - 8) in the chemotherapy-only arm.
• The 24-month progression-free survival rate was 35% (21.7 - 48.3) in the chemoradiotherapy arm and 3.6% (0 - 9.7) in the chemotherapy arm, HR: 0.36.

In conclusion, this is the first prospective study to demonstrate the clear effect on 2-year overall and progression-free survival of adding consolidation radiotherapy using the IMRT technique at the tumor site to standard chemotherapy in patients with metastatic nasopharyngeal cancer at diagnosis who responded well after 3 cycles of induction chemotherapy. These results are of a nature to change clinical practice and international guideline recommendations.