Study Shows First Line Keytruda Treatment Effective for Head & Neck Cancer
by Dr. C.H. Weaver M.D. 9/20/2018
Multiple clinical trials have now demonstrated that the PD-1 checkpoint inhibitor Keytruda (pembrolizumab) immunotherapy significantly improves the treatment of head and neck cancers and extends overall survival when used as first-line treatment for advanced head and neck carcinomas in patients expressing PD-L1.
About Head and Neck Cancer
Globally, head and neck cancer is the seventh most common type of cancer with an estimated 400,000-600,000 diagnoses every year. Head and neck squamous cell cancer (HNSCC) refers to head and neck cancer that originates in certain cells called squamous cells.
Metastatic or stage IV head and neck cancer refers to cancer that has spread from its site of origin to distant sites in the body. Overall survival at 5 years for patients diagnosed with metastatic head and neck cancer had remained less than 4%, indicating a significant need in improved treatment for patients with this disease.
Head and neck cancers originate in the tissues in or around the mouth, nose, and throat. Risk factors for head and neck cancer include smoking, alcohol consumption, and infection with high-risk types of human papillomavirus (HPV). Patients with head and neck cancer that has spread to other parts of the body or that has returned after initial treatment have limited treatment options, and researchers continue to explore new and more effective approaches to treatment.
Keytruda belong to a new class of medicines called PD-1 inhibitors that have generated great excitement for their ability to help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses, allowing cancer cells to evade an attack by certain immune cells. Drugs that block the PD-1 pathway enhance the ability of the immune system to fight cancer.
What do the Studies Show?
Keytruda as First Line Treatment: KEYNOTE 048
The pivotal Phase III KEYNOTE-048 trial, demonstrated that Keytruda resulted in significantly longer survival compared to Erbitux (cetuximab) in combination with platinum chemotherapy plus 5-Fluorouracil (5-FU), the previous standard first line treatment for HNSCC.
“This interim analysis of KEYNOTE-048 trial showed that Keytruda monotherapy has the potential to help patients with head and neck cancer whose tumors express high-levels of PD-L1,” said Dr Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
The final results of KEYNOTE -048 have now been released. Commenting on the findings for ESMO, Dr Tanguy Seiwert, Head and Neck Cancer Programme Director, and Assistant Professor of Medicine at the University of Chicago Medicine, Chicago, US, said: “This is the first study to show superior overall survival over the decade-old standard of care, platinum-based chemotherapy and cetuximab, and establishes PD-L1 CPS as a valid marker for head and neck cancer that should be routinely measured in these patients.”
Keytruda is already approved to treat patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Keytruda® in Advanced Head and Neck Cancer: KEYNOTE 012
Initial findings were presented at 2015 Annual Meeting of the American Society of Clinical Oncology (May 29–June 2, Chicago, Illinois) and published in the Journal of Clinical Oncology.
According to researchers the clinical trial known as KEYNOTE 012 demonstrated that Keytruda was active in a type of recurrent or metastatic head and neck cancer that originates in cells known as squamous cells. Patients received Keytruda at a dose of 10 mg/kg every two weeks. Those who tested positive for tumor biomarkers that indicated the presence of PD-L1—a ligand (or molecule) of the protein that Keytruda inhibits—had 20% response rate to treatment.
As part of additional research with the KEYNOTE 012 study, researchers gave patients 200 mg of Keytruda every three weeks. They did not take into account PD-L1 expression when they evaluated results (meaning that study outcomes include patients with tumors that were positive and negative for PD-L1). Patients were monitored with X-rays every two months. This research included 132 patients with recurrent or metastatic squamous cell head and neck cancer. The current results include 99 of these patients.
Of the 99 patients evaluated, 18% responded to treatment with Keytruda. Of these patients, 18 patients had a partial response and 31% had stable disease.
Almost half of all participating patients experienced side effects related to treatment with Keytruda. Side effects tended to be mild and included fatigue, decreased appetite, fever, and rash.
These results led to the FDA approval of Keytruda
Keytruda® Approved for Treatment of Advanced Head and Neck Cancer
The United States Food and Drug Administration (FDA) originally approved Keytruda® for the treatment of advanced head and neck cancer that has stopped responding to platinum-based chemotherapy agents.
Results from long-term follow-up data from the KEYNOTE-012 trial that led to the final approval of pembrolizumab in head and neck cancer were presented at this year’s annual meeting of the American Society of Clinical Oncology (ASCO).2 The trial evaluated the effectiveness of Keytruda in the treatment of 192 patients with metastatic or recurrent HNSCC.
- Anti-cancer responses were achieved in 18% of patients.
- 85% of anti-cancer responses lasted for at least 6 months, and 71% of anti-cancer responses lasted for at least one year.
- At 6 months after initiation of treatment with pembrolizumab, 58% of patients were alive, and 25% of patients were alive with no progression of cancer.
- At one year after initiation of treatment with pembrolizumab, 38% of patients were alive, and 17% of patients were alive with no progression of cancer.
- Patients who achieved anti-cancer responses with pembrolizumab had been followed for a median time of 12.5 months at the time of data collection. The median duration of time that anti-cancer responses continued had not yet been reached.
- Pembrolizumab was generally well tolerated.
This approval provided another treatment option for patients with advanced squamous cell head and neck cancer that has stopped responding to standard therapeutic options.
Merck. Corporate News. FDA approves Merck’s Keytruda® (pembrolizumab) for patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. Available at: . Accessed August 8, 2016.
Mehra R, Seiwert T, Mahipal A, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): Pooled analyses after long-term follow-up in KEYNOTE-012. Proceedings from the 201 annual ASCO meeting. Abstract #6012. Available at: . Accessed June 7, 2016.
Seiwert TY, Haddad RI, Gupta S, et al. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): Preliminary results from KEYNOTE-012 expansion cohort. Journal of Clinical Oncology. 33, 2015 (supplement; abstract LBA6008).
Seiwert TY, Barbara Burtness B, Weiss J, et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV–associated head and neck (H/N) cancer. Journal of Clinical Oncology. 32:5s, 2014 (supplement; abstract 6011)
Abstract LBA8_PR ‘First-line pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC): interim results from the phase 3 KEYNOTE-048 study‘ will be presented by Barbara Burtness during the Presidential Symposium 3 on Monday, 22 October, 16:30 to 18:00 CEST in Room 18 - Hall A2. Annals of Oncology, Volume 29 Supplement 8 October 2018