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Expert Sheds Light on Exploration of Novel Agents for Head and Neck Cancer

Gina Columbus
Published Online:2:17 PM, Thu May 4, 2017

Aarti Bhatia, MD

While the PD-1 inhibitors pembrolizumab (Keytruda) and nivolumab (Opdivo) have generated excitement in the field of head and neck cancer, the agents do not demonstrate durable responses or even clinical activity in all patients. In an effort to improve this, researchers are actively studying novel agents and combination regimens in hopes of improving survival.

For example, CDK4/6 inhibitors palbociclib (Ibrance) and ribociclib (Kisqali)—both approved in breast cancer–are being tested in combination with cetuximab (Erbitux) in the head and neck cancer population. For palbociclib, researchers are testing the CDK4/6 inhibitor with cetuximab versus cetuximab alone in HPV-negative, cetuximab-naïve patients with recurrent or metastatic disease to see whether there is an improvement in overall survival (OS) in a phase II trial (NCT02499120).

The phase I trial exploring ribociclib with cetuximab in 12 patients with recurrent or metastatic disease has a primary endpoint of maximum-tolerated dose with ribociclib doses of 400 mg and 600 mg (NCT02429089). In an expansion part, objective response rate, progression-free survival and OS will be calculated with the inclusion of 14 patients.

Buparlisib (BKM120) is another targeted therapy demonstrating promise. Results of the phase II BERIL-1 trial were presented at the 2016 ASCO Annual Meeting, in which the addition of the pan-PI3K inhibitor to chemotherapy reduced the risk of disease progression or death by 35% in patients with advanced head and neck squamous cell carcinoma.

In an interview with Targeted Oncology, Aarti Bhatia, MD, assistant professor of medicine (medical oncology), Yale School of Medicine, highlights the newer single agents and combination treatments being investigated for patients with head and neck cancer.

TARGETED ONCOLOGY:  Can you start by discussing where we are as far as treatments for head and neck cancer and any recent advancements?

Bhatia: I spoke about all of the targeted therapies that have been approved and that we have been using for many years. Additionally, I shed light on some of the novel drugs that have been tested in the past few years, and I talked about novel drugs in development and how we can improve outcomes for these patients. 

TARGETED ONCOLOGY:  What agents are in the pipeline that look promising?

Bhatia: Within the past couple of years, afatinib (Gilotrif) has been tested in the metastatic setting and in the adjuvant setting. Those data will be out at the 2017 ASCO Annual Meeting. It also being tested in combination with other ErbB family receptor inhibitors.

I spoke about buparlisib and data on it from the BERIL-1 trial was reported at the 2016 ASCO Annual Meeting. In the metastatic recurrent population, it showed encouraging results in combination with chemotherapy in the second-line setting for platinum-refractory patients. Those are some of the recent data and we expect more of these drugs to have results in the near future. 

In addition, there are other oncogenic aberrations that have been reported from other studies. There are a variety of drugs, which are in development in early-stage trials, such as MET inhibitors in combination with cetuximab (Erbitux). There are CDK4/6 inhibitors [being explored]; palbociclib and ribociclib, which are 2 for breast cancer, are being tested with cetuximab. We are opening a trial at Yale Cancer Center with PARP inhibitors for the HPV-positive patients with head and neck cancers, and we will see some data come out of that.

We are also opening an afatinib plus cetuximab study at Yale Cancer Center that will open for accrual for recurrent metastatic patients. Data from all of these trials will be exciting and results will be forthcoming in a few years. 

TARGETED ONCOLOGY:  What are some remaining challenges in this space that you would like to see answered in the next 5 to 10 years?

Bhatia: The biggest question unanswered is, does targeting these mutations we find in patients offer any benefit to them? The NCI’s MATCH trial would be a good trial to answer that question. People are enrolled on that trial after failure on standard treatment options. It will be interesting to see whether people have a benefit, and if they have any side effects. That would be 1 way to answer the question.

TARGETED ONCOLOGY:  What ongoing trials do you believe will show promise in this space?

Bhatia: In addition to the advances in the metastatic recurrent setting, there is also immunotherapy in combination [being studied] in the locally advanced setting. We would like to see the results of those trials. There are combination strategies with immunotherapies with drugs that help to overcome resistance to immunotherapy, so those trials will be up and coming. 

I am also very interested in having a focus on [preventing chemotherapy]: can we [avoid] chemotherapy? What drugs will help with that? There are other prevention strategies that we also need to be working more on. Those are some things that I am interested in. 
Soulières D, Faivre SJ, Mesia R, et al. BERIL-1: a phase II, placebo-controlled study of buparlisib (BKM120) plus paclitaxel in patients with platinum-pretreated recurrent/metastatic head and neck squamous cell carcinoma (SCCHN). J Clin Oncol. 34, 2016 (suppl; abstr 6008).

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