Treatment recommendations retained for locally advanced NPC, but challenges remain
Current guidelines for treating locoregionally advanced nasopharyngeal carcinoma (NPC) maintain that concomitant cisplatin-radiotherapy (RT) is the standard of care for stage II and above, adjuvant cisplatin and 5-fluorouracil (5-FU) therapy may be beneficial and the use of induction chemotherapy remains controversial, according to Professor Anthony TC Chan of the Chinese University of Hong Kong.
In his discussion at the ESMO Asia 2016 Congress in Singapore, Chan reviewed current treatment recommendations in the context of findings of recent studies involving commonly administered regimens for locally advanced NPC, which typically includes stages III, IVA and IVB.
“The standard treatment is intensity-modulated radiotherapy (IMRT), but the question is how to incorporate chemotherapy in the best manner for each of our patients,” Chan said.
The evidence for the concurrent use of cisplatin and radiotherapy is robust enough, with studies demonstrating improvements in survival outcomes. In addition, cisplatin is effective regardless of whether it is given weekly or every 3 weeks “so long as cumulatively, you give 200 mg/m2,” he added.
Chan discussed findings from randomized controlled trials using concomitant chemoradiotherapy versus radiotherapy alone. Concurrent therapy with or without adjuvant therapy with cisplatin appeared to have better outcomes in terms of overall survival (OS), progression-free survival, distant metastasis and locoregional control.
“Theoretically, concurrent [chemoradiotherapy] is meant to be better for locoregional control but in fact, it’s not quite like that,” said Chan. “In NPC, a very chemosensitive disease, it would appear that so long as you give adequate doses of cisplatin during the radiotherapy, it has benefit on distant metastases as well. And adjuvant is just supposed to be mostly helping distant [metastasis], but it doesn’t entirely appear to be that way, either. So it’s really quite difficult.”
According to Chan, there is a caveat to evidence suggesting that concurrent and adjuvant therapy may be better than concurrent chemoradiotherapy alone.
“Concomitant and adjuvant trials all had pretty much the same chemotherapy during radiotherapy, which is cisplatin, whereas the concomitant-only [studies] actually had several trials that did not use cisplatin so it was not as optimal,” Chan explained.
Chan reported findings from a study by Lee and colleagues, which showed that compared with radiotherapy alone, concurrent plus adjuvant therapy statistically significantly reduced treatment failure and cancer-specific deaths. However, the increase in cancer deaths narrowed the resultant gain in OS even though there was no statistically significant increase in major late toxicity. [J Natl Cancer Inst 2010;102:1188-98]
“Was that related to the toxicities? It’s very hard to tease out,” said Chan. “When we face patients after the chemoradiation, to persuade all of them to have three more cycles of platin and 5-FU is indeed very tough.”
Risk stratification using Epstein Barr Virus (EBV) DNA as a biomarker in NPC also appears promising, according to Chan. He discussed the NRG-HN001 study protocol, which investigates the use of EBV DNA in individualizing treatment for NPC. This includes a phase III noninferiority trial comparing OS outcomes between patients receiving and not receiving adjuvant cisplatin plus 5-FU therapy.
Chan noted that the presence of EBV DNA after therapy is a strong predictor of treatment failure. “The NRG study would really probably address once and for all the low-risk undetectable EBV DNA after treatment and whether it’s okay to leave out the adjuvant,” he said.
Lastly, Chan addressed the question of whether induction chemotherapy is recommended for locally advanced NPC. “One of the big dangers of neoadjuvant therapy or induction is if the tumour shrinks or if the patient feels very good, he or she doesn’t want to go through chemoradiation, particularly chemo; [it’s] even worse if they don’t go through radiation,” he said. “Many of them don’t want more chemo.”
Based on conflicting results from several studies comparing concurrent chemoradiotherapy with different neoadjuvant regimens, Chan recommends going back to the current ESMO guidelines—induction therapy is not the standard of care, but may still be given.
“As we have really good concurrent cisplatin-IMRT, we probably don’t need neoadjuvant induction for locoregional,” he said, adding that more evidence is needed to establish the use of induction therapy in NPC.