Chemo Prior to CRT in Nasopharyngeal Carcinoma May Improve Outcomes

The addition of two cycles of neoadjuvant chemotherapy to concurrent chemoradiotherapy improved tumor control in patients with nasopharyngeal carcinoma.

The addition of two cycles of neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CRT) improved tumor control compared with concurrent CRT alone in patients with locally advanced nasopharyngeal carcinoma (NPC), according to a new study. Overall survival, however, was not improved, and the study had some limitations that make conclusions difficult to draw (abstract 6005).

“As we all know, NPC is very sensitive to chemotherapy and radiotherapy,” said Ming-Yuan Chen, a professor at Sun Yat-Sen University Cancer Center in Guangzhou. The researchers sought to determine whether NACT prior to concurrent CRT might improve outcomes.

Chen presented results of this phase III randomized trial at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting. A total of 476 patients were randomized to receive either concurrent CRT alone (238 patients) or concurrent CRT following two cycles of cisplatin and fluorouracil (NACT plus concurrent CRT; 238 patients). Patients were generally well matched; most were men, and the median age in the two groups was 42 and 44 years.

In the intention-to-treat analysis, the NACT plus concurrent CRT group achieved a better disease-free survival (DFS) rate. At 3 years, this rate was 82.0% with NACT and 74.1% without it (P = .028). The distant metastasis–free survival rate (DMFS) had a trend toward improvement with NACT (P = .056), and in a per-protocol analysis this did reach significance (P = .041). The DFS rate was also significantly better with NACT plus concurrent CRT in the per-protocol analysis (P = .006).

Overall survival, however, was no different in the intention-to-treat analysis (P = .815); the same was true for locoregional relapse–free survival (LRRFS; P = .0430). In the per-protocol analysis, overall survival was significantly better with NACT (P = .006), as was LRRFS (P = .041).

On a multivariate analysis, NACT plus concurrent CRT remained significantly better than concurrent CRT alone with regard to DFS, with a hazard ratio of 0.670 (95% CI, 0.474–0.946; P = .023). The same was true for DMFS, but not for overall survival or for LRRFS.

Chen noted that 15 patients in the concurrent CRT arm withdrew consent before treatment, and 11 of those patients received NACT, which could have influenced the intention-to-treat analysis.

Clearly, only those patients receiving NACT experienced any toxicity during the NACT period; grade 3/4 events of interest included neutropenia, leukopenia, and vomiting. During the concurrent CRT period, more of the NACT plus concurrent CRT patients experienced grade 3/4 anemia, and numerically more of several other adverse events but not to a statistically significantly different level.

“Based on our data, we think the addition of two cycles of neoadjuvant…chemotherapy to concurrent CRT could improve tumor control compared with concurrent CRT alone in locoregionally advanced NPC, particularly at distant sites, but longer follow-up is expected,” Chen concluded.

Robert I. Haddad, MD, of the Dana-Farber Cancer Institute in Boston, was the discussant for the session, and he said that this study adds to a growing body of literature suggesting that NACT is useful in this setting. Another phase III trial yielded a positive result in 2016, he said, and guidelines should now change to reflect the available data on this treatment for NPC patients.