IMRT Alone is Non-Inferior to CCRT in Nasopharyngeal Carcinoma

Radiotherapy alone yielded non-inferior overall survival (OS) and failure-free survival (FFS) rates vs radiotherapy with concurrent chemoradiotherapy (CCRT) in patients with low-risk nasopharyngeal carcinoma, according to final OS data from a phase 3 trial (NCT02633202) presented at the 2024 ASCO Breakthrough Conference.¹

At a median observation time of 44 months (IQR, 32-58), the HR for FFS, which represented the study's primary end point, was 1.36 (95% CI, 0.70-2.66; P = .85). Additionally, at a median follow-up of 70.1 months, the 5-year OS rate was 95.2% among patients who received intensity-modulated radiation therapy (IMRT) alone (n = 172) vs 98.2% among patients who received the current standard-of-care of CCRT (n = 169; HR, 2.27; 95% CI, 0.70-7.40; P = .16). The difference in 5-year FFS rates was not statistically significant, at 86.2% compared with 88.4%, respectively (HR, 1.16; 95% CI, 0.64-2.07; P = .63). Subgroup analysis data also showed that OS results were consistent across patient subgroups, including N categories and disease stages.^1,2

“This low-risk nasopharyngeal carcinoma subgroup can be safely treated with IMRT alone instead of CCRT which provides non-inferior survival and disease control [and] reduces toxicities and improves quality of life. Our trial supports IMRT alone as a valid option for [patients with] low-risk T1-2N1 and T3N0 nasopharyngeal carcinoma,” Rui Guo, MD, of the Department of Radiation Oncology at Sun Yat-sen University Cancer Center in China, said during the presentation.

Late treatment-related toxicities in the safety populations of the IMRT alone arm (n = 165) vs the chemoradiation arm (n = 169) occurred at grade 1 (77.5% vs 81.0%), 2 (38.7% vs 51.4%), and 3 to 4 (4.84% vs 2.95%). Notably, hearing impairment according to the Hearing Handicap Inventory for Adult-Screening (HHIA-S) criteria showed that hearing impairment was more prevalent in the chemoradiation arm (39.4%) compared with the IMRT alone arm (29.6%). Patients treated with IMRT experienced mild (22.2%) and severe (7.4%) hearing impairment whereas those in the chemoradiation arm experienced increased rates of mild (28.9%) and severe (10.5%) hearing impairment. Mild impairment was defined as a total score of 8 to 24 and above 24 was defined as severe per HHIA-S criteria.¹

“Our previous results showed that IMRT alone [demonstrated] non-inferior 3-year FFS compared with chemoradiotherapy—90.5% vs 91.9%, respectively—with a difference which matched the non-inferiority margin,” Guo said. “During the entire treatment course there was a significantly lower incidence of reported grade 3 or 4 adverse effects [AEs] in the IMRT alone group compared with chemoradiotherapy.”

Investigators conducted the randomized, open-label, non-inferiority trial at 5 hospitals in China to examine CCRT, the standard treatment for patients with stage II nasopharyngeal carcinoma, as cisplatin-based CCRT increases severe acute AEs and late occurring toxicities. Guo noted that “supportive evidence related to the roles of CCRT was based on 2D-CRT. High-level evidence regarding the role of chemotherapy for this population in the IMRT era is lacking.”

Patients enrolled in the study had low-risk nasopharyngeal carcinoma which was defined as stage II/T3N0M0 disease without adverse features including all nodes less than 3 cm, no level IV/Vb nodes, no extranodal extension, and Epstein-Barr virus DNA of less than 4000 copies/mL.¹ CCRT consisted of IMRT given with cisplatin 100 mg/m² every 3 weeks for 3 cycles. The recommended dose of IMRT was 69 to 70 Gy at 2.0-2.2 Gy per fraction administered once daily in 5 fractions every week.³

Baseline patient characteristics were well-balanced between the investigational and control arms; the median age was 48 years (range, 22-65) vs 48 years (range, 23-65), respectively. Most patients in the IMRT alone arm vs CCRT arm were male (68% vs 72%) and had parapharyngeal involvement (71% vs 68%). Disease stages included T2N0 (16% vs 12%), T3N0 (25% vs 26%), T1N1 (21% vs 20%), and T2N1 (38% vs 42%), respectively.³

Further data showed that the most common grade 1 late treatment-related AEs in the investigational and control arms included dry mouth (49.6% vs 43.1%), auditory/hearing (36.9% vs 41.4%), skin/neck tissue damage (24.2% vs 32.5%), hypothyroidism (14.5% vs 25.4%), and peripheral neuropathy (7.87% vs 15.3%), respectively. Grade 3 to 4 late treatment-related AEs occurring in the IMRT arm vs chemoradiation arm included hypothyroidism (2.42% vs 0.59%), dry mouth (1.21% vs 1.18%), auditory/hearing (0.60% vs 1.18%), and skin/neck tissue damage (0.60% vs 0.0%), respectively.¹

Disclosures: This research was funded by the National Natural Science Foundation of China,Natural Science Foundation of Guangdong Province, Key-Area Research and Development Program of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Sun Yat-Sen University Clinical Research 5010 Program, and the National Key Research and Development Program of China.

References

1. Guo R, Zhang Y, Zhang N, et al. Radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy in patients with low-risk nasopharyngeal carcinoma: Updated results from a multicenter, open-label, non-inferiority, randomized phase III trial. J Clin Oncol. 2024;42(suppl 23):142. doi:10.1200/JCO.2024.42.23_suppl.142
2. ASCO breakthrough to highlight advances in esophageal, nasopharyngeal, lung, cancers new treatment approaches help improve survival, quality of life. News release. ASCO. August 5, 2024. Accessed August 6, 2024. https://society.asco.org/about-asco/press-center/news-releases/asco-breakthrough-highlight-advances-esophageal-nasopharyngeal
3. Tang LL, Guo R, Zhang N, et al. Effect of radiotherapy alone vs radiotherapy with concurrent chemoradiotherapy on survival without disease relapse in patients with low-risk nasopharyngeal carcinoma: A randomized clinical trial. JAMA. 2022;328(8):728-736. doi:10.1001/jama.2022.13997