Nasopharyngeal cancer (NPC) is the most common head and neck cancer in South China and South
East Asia. Worldwide, there are 80,000 incident cases and 50,000 deaths annually. In Hong
Kong, NPC ranked as the tenth most common cancer in man. Up to 30% of NPC patients will
develop recurrence or metastases after primary radiotherapy or chemoradiation. Platinum-based
chemotherapy regimen has been the main stay of first line treatment for recurrent or
metastatic NPC. However, the duration of response is short and currently there is no
recommended standard second line chemotherapy. Axitinib is a highly potent and selective
inhibitor of VEGF receptor. Selectively targeting a single growth factor receptor pathway
provides the potential to rationally adjust dosages and combine drugs directed at specific
parts of the pathway to minimize toxicity and achieve the optimum therapeutic benefit. In the
phase 2 axitinib monotherapy in recurrent or metastatic NPC who failed at least one line of
chemotherapy, the clinical benefit rate (CBR, complete response + partial response + stable
disease) was 78.4% at 3 months but decreased to 43.2% at 6 months. However, the confirmed
objective response rate (ORR) by RECIST was only 2.7% and unconfirmed ORR of 18.9%, with no
complete response.Recently, the promising clinical activity of immune check point inhibitors
has been demonstrated in NPC. The ORR was 25.9% (7 partial responses out of 27 patients) for
single agent pembrolizumab, and 20.5% (including 1 complete response and 7 partial responses
out of 44 patients) for single agent nivolumab,9 in recurrent or metastatic NPC who failed at
least first line chemotherapy.
The combination of axitinib and avelumab has been studied in renal cell carcinoma (RCC).
Based on the above promising and positive results in renal cell carcinoma (RCC) and head and
neck squamous cell carcinomas (HNSCC), the investigators hypothesize that the combination of
axitinib and avelumab in the second line setting of NPC will achieving a more complete, deep
and durable response than either agent alone, without a significant increase in toxicity.
This is an open-label, single arm, phase 2 clinical trial evaluating the activity and safety
of the combination of axitinib and avelumab in recurrent or metastatic NPC patients who
failed at least one line of platinum-based chemotherapy.