Nancy Y. Lee, MD, discusses the ongoing JAVELIN HEAD AND NECK 100 trial and the overall impact of immunotherapy for patients with head and neck cancer.
Nancy Y. Lee, MD
Investigators are aiming to measure the impact of immunotherapy as an addition to standard chemotherapy plus radiation therapy in patients with locally advanced squamous cell carcinoma of the head and neck in the phase III JAVELIN HEAD AND NECK 100 trial.
In the ongoing study (NCT02952586), researchers are evaluating the PD-L1 inhibitor avelumab (Bavencio) in combination with standard-of-care cisplatin plus radiotherapy versus standard-of-care alone in the first-line setting.
Eligible patients have stage III to IVb locally-advanced squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx, and are HPV-negative or nonoropharyngeal HPV-positive. Patients who have HPV-positive oropharyngeal disease that is T4, N2c, or N3 are eligible, as well.
All patients will receive cisplatin (100 mg/m2) plus intensity modulated radiation therapy with either avelumab (10 mg/kg IV) or placebo. Progression-free survival is the primary endpoint of the trial, with secondary endpoints being overall survival, objective response rate, duration of response, distant metastatic failure, and locoregional failure.
In an interview with OncLive, lead study author Nancy Y. Lee, MD, vice chair of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, discussed the ongoing JAVELIN HEAD AND NECK 100 trial and the overall impact of immunotherapy for patients with head and neck cancer.Lee: The trial is for HPV-negative, locally advanced head and neck cancer, but it is also for very advanced HPV-positive head and neck cancer. These are very advanced patients. It is a randomized phase III trial of 640 patients comparing standard of care, which is high-dose cisplatin and fractionary radiation of 70 Gy, versus standard of care plus avelumab.
We know that the FDA has approved 2 drugs, pembrolizumab (Keytruda) and nivolumab (Opdivo), in first- or second-line metastatic recurrent head and neck cancer. It has been shown that immunotherapy, as a single agent, can improve overall survival. The overall response rate is 13% to 17%. Therefore, we want to bring it upfront to the definitive setting in locoregional advanced head and neck cancer—hence, the rationale of the trial.
The trial is ongoing, and we have about 50 patients [enrolled]. There are some ongoing trials and, so far, preliminary data do not show any enhanced side effects with this combination of immunotherapy on top of standard of care.
It will be interesting to see what a PD-L1 inhibitor has to bring to the table, as we have seen what PD-1 inhibitors pembrolizumab and nivolumab can do for this population.
And, in the definitive setting too. What Pfizer decided to do is to go to the locoregionally advanced setting.
I don’t think we should expect any differences, because we are targeting sort of the similar area. Although, I am personally curious to know whether there is less toxicity. This is because we are going after the tumor instead of the immune cell. We select and enrich for the very sick and advanced patients, where the locoregional control is not 90%; it’s really in the order of the 50% to 70% range. For the HPV-positive patients—the T4 N2c, which are the worst comers—the control rate is 60% to 70%. My thinking is that by adding anti—PD-L1 therapy, we can enhance the effect of locoregional control. However, what I am personally interested in is to see the adjuvant phase where patients’ distant metastases can be mitigated, which is another battle that we have in this disease. It has made a difference. I've seen patients [who remain] alive whereas, in the past, they would have not made it and been dead from their disease. Therefore, we have altered the longevity of these patients.
Furthermore, what is interesting is that after you give immunotherapy, somehow, the whole makeup of the patient is different. Let’s say they fail immunotherapy, and then you give systemic therapy afterwards, and somehow the patients you didn’t think would respond to a therapy like methotrexate are responding. That is very exciting. Somehow, the immunotherapy is changing the makeup of the patient and they are responding to drugs differently.The entry criteria are for HPV-negative patients where the outcome is not great and also the high-risk HPV-positive patients—the T4 N2c patients. We really need patients enrolled on the trial so we can find out the answer [to this question]: what is immunotherapy going to do on top of standard of care? We hope it will make a difference. I think [it might] because it is enriched.
Lee NY, Ferris RL, Beck JT, et al. JAVELIN head and neck 100: A phase 3 trial of avelumab in combination with chemoradiotherapy (CRT) vs CRT for 1st-line treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). J Clin Oncol. 2017;35 (suppl; abstr TPS6093).