Keytruda Precision Cancer Immunotherapy Treatment for Head & Neck Cancer

Keytruda immunotherapy is effective treatment for newly diagnosed and recurrent head and neck cancers.

by Dr. C.H. Weaver M.D. 6/2019

Multiple clinical trials have now demonstrated immunotherapy with the PD-1 checkpoint inhibitor Keytruda (pembrolizumab) significantly improves overall survival when used as first-line treatment for advanced head and neck carcinomas in patients expressing PD-L1. The final results of the KEYNOTE -048 clinical trial were released at the American Society of Clinical Oncology annual meeting in Chicago, June 2019 and demonstrate superior overall survival compared to the decade-old standard of platinum-based chemotherapy and Erbitux (cetuximab). Keytruda as a single drug, and in combination with chemotherapy was found to produce superior survival when compared to chemotherapy in all patients who tested positive for PD-1 or PD-L1. All patients should undergo testing and the results of this trial led to FDA approval of Keytruda for patient that tests positive in all clinical settings.

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.

About Keytruda

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 clinical trial evaluated treatment with single agent Keytruda or Keytruda combined with chemotherapy to treatment with chemotherapy alone and demonstrated that Keytruda produced significantly longer survival compared to Erbitux (cetuximab) in combination with platinum and 5-Fluorouracil (5-FU) chemotherapy, the previous standard first line treatment for HNSCC.

KEYTRUDA in combination with chemotherapy reduced the risk of death by 40% in patients whose tumors expressed PD-L1 with CPS≥20, and prolonged survival to 14.7 months compared with 11 months for cetuximab with carboplatin or cisplatin plus 5-fluorouracil chemotherapy.

New findings for the CPS ≥1 population showed KEYTRUDA in combination with chemotherapy reduced the risk of death by 35% and prolonged survival by 3 months compared with chemotherapy alone. Treatment with single agent KEYTRUDA produced a similar survival benefit to that achieved with chemotherapy.

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

These results were recently updated at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO).

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.

Long-Lasting Responses Achieved with Keytruda® in Advanced Head and Neck Cancer

Results from long-term follow-up of data from the KEYNOTE-012 trial were presented at this year’s ASCO. 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 keytruda, 58% of patients were alive, and 25% of patients were alive with no progression of cancer.
  • At one year after initiation of treatment with keytruda, 38% of patients were alive, and 17% of patients were alive with no progression of cancer.
  • Patients who achieved anti-cancer responses with keytruda 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.

These results provide further evidence that treatment with keytruda can provide long-lasting anti-cancer responses, while being well tolerated, among patients with metastatic and recurrent HNSCC.

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.

References:

  1. 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: http://www.mercknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-keytruda-pembrolizumab-patients-recurr-0. Accessed August 8, 2016.
  2. 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: http://abstracts.asco.org/176/AbstView_176_168015.html. Accessed June 7, 2016.
  3. 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).
  4. 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)
  5. 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
  6. <a href="https://investors.merck.com/news/press-release-details/2018/KEYTRUDA-pembrolizumab-Monotherapy-Met-a-Primary-Endpoint-in-the-Phase-3-KEYNOTE-048-Trial-Significantly-Improving-OS-as-First-Line-Therapy-in-Head-and-Neck-Squamous-Cell-Carcinoma-Patients-Whose-Tumors-Expressed-PD-L1-CPS-20/default.aspx">https://investors.merck.com/news/press-release-details/2018/KEYTRUDA-pembrolizumab-Monotherapy-Met-a-Primary-Endpoint-in-the-Phase-3-KEYNOTE-048-Trial-Significantly-Improving-OS-as-First-Line-Therapy-in-Head-and-Neck-Squamous-Cell-Carcinoma-Patients-Whose-Tumors-Expressed-PD-L1-CPS-20/default.aspx</a>
  7. https://mavendoctors.io/cancerconnect/head-neck-cancer/keytruda-approved-for-advanced-head-and-neck-cancer-y2EdIGqND0iR0mMoG0cykw/
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