Radiotherapy Improves Overall Survival in Metastatic Nasopharyngeal Carcinoma

By Will Boggs MD

August 05, 2020

NEW YORK (Reuters Health) - Locoregional radiotherapy added to chemotherapy improves overall survival in patients with de novo metastatic nasopharyngeal carcinoma (mNPC), according to new research.

"For chemotherapy-sensitive patients with de novo mNPC, systemic chemotherapy alone might not be the best treatment, and combined high-dose locoregional radiotherapy should be adopted to further improve the overall survival of these patients," Dr. Ming-Yuan Chen of Sun Yat-sen University Cancer Center, in Guangzhou, China, told Reuters Health by email.

Chemotherapy with gemcitabine and cisplatin is the current standard of care for first-line treatment of NPC. Retrospective studies have shown improvement in overall survival with combination radiotherapy and systemic therapy for patients with mNPC.

Dr. Chen and colleagues undertook a multicenter phase-3 randomized controlled trial to investigate the efficacy of locoregional radiotherapy to the primary tumor and nodal regions. They enrolled 126 patients with mNPC who demonstrated an initial complete or partial response to palliative chemotherapy with fluorouracil and cisplatin (which were the standard of care when the study began).

During a median follow-up of 26.7 months, the 24-month overall survival was 76.4% in patients receiving chemotherapy plus radiotherapy and 54.5% in the chemotherapy-alone group, the team reports in JAMA Oncology.

Patients in the radiotherapy group had a 58% reduced hazard of death (P=0.004) and a 64% reduced hazard of progression (P<0.001), compared with patients in the chemotherapy-only group.

The treatment groups did not differ in the rates of hematologic, hepatic, renal, or gastrointestinal toxic effects. Radiotherapy was associated with grade-3-or-higher mucositis in 33.9% of patients, acute grade-3-or-higher dermatitis in 8.1%, and grade-3-or-higher xerostomia in 6.5%.

"This trial has further changed our traditional understanding that patients with metastatic disease may undergo palliative radiotherapy for pain and other symptom control," Dr. Chen said. "According to this study, we observe that locoregional radiotherapy resulted in superior overall survival outcomes and fewer distant metastatic recurrences (54.0% vs. 68.3%). These observations suggest (that) targeting the primary tumor lesion could delay the seeding of subsequent tumor clones at distant sites, which might (explain) the increased overall survival rate."

Dr. Nancy Lee of Memorial Sloan Kettering Cancer Center, in New York, who coauthored a linked commentary, told Reuters Health by email, "I think we now have level-I evidence to demonstrate the importance of locoregional control for our patients. Furthermore, unlike other disease sites, obtaining locoregional control is important for nasopharyngeal cancer, as progression of disease locally can result in unacceptable symptoms for our patients."

"I think we need to educate our colleagues of the findings of this trial, and we need to work more closely with our medical oncology colleagues to deliver locoregional therapy for these patients who present with mNPC," she said.

Dr. Lee added, "The next step is to see what additional benefit we can see from the addition of radiotherapy to metastatic foci and how we can integrate radiotherapy not only to the primary site but also to these metastatic foci with the goal of further improving survival. We see the survival benefits in other cancers."

Dr. Jun Ma of Sun Yat-sen University Cancer Center, who recently reviewed nasopharyngeal carcinoma but was not involved in this study, told Reuters Health by email, "As gemcitabine plus cisplatin (GP) is now the first-line chemotherapy in recurrent and metastatic NPC, combination of systemic GP and high-dose locoregional radiotherapy should be the new standard of care in advanced NPC patients."

"Understanding the mechanisms contributing to this synergistic effect in de novo metastatic NPC is highly important," he said. "We wonder whether consolidative treatment to metastatic sites could further improve survival outcome in these patients. This should be explored in future trials."

The study had no commercial funding, and the researchers report no conflicts of interest.

SOURCE: https://bit.ly/2Xb1kEE and https://bit.ly/2PceaOD JAMA Oncology, online July 23, 2020.

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