Head & Neck Cancer: New Standard for Metastatic Disease?


Adding local radiation to systemic chemotherapy significantly improved overall survival compared with chemotherapy alone in patients with metastatic nasopharyngeal carcinoma (mNPC) who had a complete or partial response to first-line treatment, according to a multicenter randomized phase III study.

A total of 76.4% of patients with biopsy-proven metastatic disease who received combined chemotherapy with fluorouracil and cisplatin followed by intensity-modulated radiotherapy were alive at 2 years compared with 54.5% of patients assigned to chemotherapy alone, reported Melvin L.K. Chua, MBBS, FRCR, PhD, of National Cancer Centre Singapore, and colleagues.

As shown in their study online in JAMA Oncology, the trial met its primary endpoint of improved overall survival, with the combined treatment resulting in a 58% reduction in the risk for death (stratified HR=0.42; 95% CI 0.23-0.77; P=0.004).

“This study has defined a new standard of care for patients with metastatic nasopharyngeal carcinoma,” Chua told MedPageToday. “These patients are treated with first-line chemotherapy, and if patients achieve a response to chemotherapy after three to four cycles, high-dose local radiotherapy to the primary tumor should be offered as a standard of care.”

Combined chemotherapy and radiotherapy also resulted in significantly improved progression-free survival rates compared with chemotherapy alone (stratified HR=0.36; 95% CI 0.23-0.57; P<0.001). The median progression-free survival for combined treatment was 12.4 months compared with 6.7 months for chemotherapy alone.

In an accompanying commentary, Nadeem Riaz, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues wrote that “not surprisingly, there was a significant decrease in patients who had local or regional recurrence as part of their first recurrence from 70% in the chemotherapy-alone arm to 16% with the inclusion of local chemoradiotherapy, which was presumably responsible for the improvement in overall survival.”

The overall response rates at the end of chemotherapy were similar in both groups (80.9% for the combined treatment vs 82.5% for chemotherapy alone). The rate of complete response was similar as well. However, at the end of radiotherapy, the combined group’s rate of complete response improved from 7.9% to 16.4% compared with 6.3% for chemotherapy alone, the researchers reported.

“This study in nasopharyngeal carcinoma — a unique head and neck cancer in Eastern and Southeastern Asia, North Africa, and the Arctic — goes a long way to support our goal to convert even stage 4 cancer into a chronic disease,” Chua said.

The rate of hematologic adverse events was similar between the two groups. Among patients who underwent radiotherapy, 8.1% had acute grade 3 or higher dermatitis, 33.9% had grade 3 or higher mucositis, and 6.5% had grade 3 or higher xerostomia.

The data “clearly establish the benefit of locoregional chemoradiotherapy in metastatic nasopharyngeal cancer and should influence the standard of care,” Riaz and co-authors wrote in their editorial, which was titled “The Importance of Locoregional Therapy in Metastatic Nasopharyngeal Cancer.”

However, they added, several questions remain about how to incorporate the findings into current clinical practice where cisplatin/fluorouracil has been replaced by gemcitabine/cisplatin, and where anti-programmed death-ligand 1 agents have shown activity.

“Given the significantly large improvement in locoregional control with radiotherapy and how highly sensitive NPC is to chemoradiation, it is unlikely these further improvements to systemic treatments will negate the benefit of radiotherapy, and may in fact increase the importance of local therapy in this setting,” the editorialists wrote. “However, the evolving landscape of regimens for first-line metastatic NPC does raise the question of what should be delivered concurrently with radiotherapy after the induction portion of treatment, especially since it is unlikely that [cisplatin/fluorouracil] will be used as induction.”

Riaz and colleagues also questioned the dose of radiotherapy used in the study, which was determined with prechemotherapy imaging data, noting that postchemotherapy measurements may have lowered the doses and decreased toxicity. Finally, they added, the role of radiotherapy to metastatic sites remains an area to be explored.


Chua and co-authors reported no conflicts of interest.

Riaz reported financial relationships with AstraZeneca, Bristol Myers Squibb, Pfizer, Illumina, and Mirati Therapeutics; one co-author reported financial relationships with Lilly, Merck, Pfizer, AstraZeneca, and REPARE Therapeutics.

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