Treatment of Recurrent Cancer of the Throat
Patients with recurrent cancer of the throat have residual cancer after initial treatment or a recurrence after an initial complete response. Recurrent throat cancer falls into one of two broad categories: 1) a cancer that returns locally or regionally and 2) metastatic recurrence, or a recurrence at a distant site. Historically, due to the lack of local disease control and the spread of the cancer, patients with metastatic disease tended to have a poor long-term survival rate, however advances in targeted precision medicines and immunotherapies are increasing disease control and providing new treatment options.
The following is a general overview of treatment for recurrent cancer of the throat. Treatment may consist of surgery, radiation, chemotherapy, targeted precision medicines, or a combination of these treatment techniques. Multi-modality treatment using two or more techniques is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
Approaches to Treatment
Local or Regional Recurrence: The cornerstone of treatment for local or regional recurrence is surgery and/or radiation therapy, and may include systemic therapy. The use of radiation/surgery is influenced by the location and size of the recurrent cancer and prior treatment. If the patient initially received radiation therapy, surgery can sometimes be utilized to control a local or regional recurrence of the cancer. If a patient was initially treated with surgery, radiation therapy or a combination of these modalities may be effective for controlling the cancer recurrence. For more information on radiation and surgery for throat cancer, go to Radiation Therapy for Head and Neck Cancers and Surgery for Head and Neck Cancers. In summary:
- Surgical resection is used if radiation therapy fails and if technically feasible.1
- Radiation therapy is used, if not previously used in curative doses that preclude further treatment, if surgery fails.
- Surgical salvage if technically feasible, when surgery fails.
- Systemic therapy with chemotherapy or other drugs is used for metastatic disease.2
Systemic therapy figures prominently in the treatment of metastatic cancer of the throat. Systemic therapy is treatment directed at destroying cancer cells throughout the body, and may include chemotherapy, targeted therapy, or immunotherapy. Most patients with metastatic throat cancer will be treated with systemic chemotherapy or immunotherapy. The goal of administering systemic therapy is to relieve symptoms, delay cancer progression and prolong survival.1
Systemic therapy may include one or a combination of drugs. Combination therapy is more commonly utilized due to improved response rates over single drugs.2 Historically, the most frequently used combination was cisplatin and 5-FU chemotherapy.1
PD-1 Inhibitors: Keytruda® (pembrolizumab) is a systemic immunotherapy that belong to a new class of drugs called PD-1 inhibitors that work by helping the immune system recognize and attack cancer cells. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 enhance the ability of the immune system to fight cancer. Keytruda works by blocking PD-1. 3,4
Results from the KEYNOTE-012 clinical trial led to the FDA granting accelerated approval of Keytruda in some head and neck cancers 5 The trial evaluated Keytruda in the treatment of 192 patients with metastatic or recurrent head and neck cancers. Overall ~20% of individuals responded to treatment and over 70% of individual responses lasted longer than one year. Keytruda is approved for patients with recurrent or metastatic head and neck squamous cell carcinoma who have experienced disease preogression on or after platinum-containing chemotherapy.
EGFR Inhibitors: The epidermal growth factor receptor (EGFR) pathway is a normal biologic pathway found in healthy cells. It is involved in regular cellular division and growth. However, certain mutations within the EGFR gene can lead to an overactive EGFR pathway, leading to the development and/or spread of cancer. These cancers are referred to as EGFR-positive. There are several FDA-approved drugs that target or block the activity of EGFR and slow cancer growth for EGFR-positive cancers.
Erbitux® (cetuximab): Monoclonal antibodies are small proteins that can locate and target cancer cells in the body that are produced in a laboratory to either kill cancer cells directly, activate the immune system to kill cancer cells, or serve as a delivery system for a radioactive isotope or a toxin which kills the cancer cells. Erbitux is a monoclonal antibody that can block EGFRs. In a comparative trial of locally advanced head and neck cancer patients, curative-intent radiation therapy alone was compared with radiation therapy plus weekly Erbitux. patients treated with Erbitux and radiation therapy demonstrated significantly improved progression-free survival.6, 7
A study known as EXTREME (ErbituX in first-line Treatment of REcurrent or MEtastatic head and neck cancer) contributed to the FDA approval of Erbitux. The study enrolled patients with metastatic or locally recurrent head and neck cancer who were not candidates for potentially curative treatment with surgery or radiation. Patients were treated with chemotherapy alone or in combination with Erbitux. The combination of chemotherapy and Erbitux improved overall survival and delayed cancer progression.8
Combined Chemotherapy and Radiation Therapy: Combined modality therapy can play a central role in the management of metastatic cancer of the throat. A German study involving 226 patients with stage III and IV cancer of the head and neck demonstrated that combining chemotherapy with radiation is more effective than treatment with radiation alone. In this study, 51% of patients who received the combination therapy lived 5 years or more after treatment, compared to 31% with radiation alone. Control of the local cancer was achieved in 66% of the patients on combination therapy, compared to 42% with radiation alone. Also, the rate of cancer recurrence was lower for the patients receiving combination therapy, 58% versus 80% with radiation alone.2
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of metastatic cancer of the throat will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active exploration to improve the treatment of metastatic cancer of the throat include the following:
PD-1 Inhibitors: Keytruda® (pembrolizumab) and Opdivo® (nivolumab) belong to a new class of drugs 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. Drugs that block PD-1 enhance the ability of the immune system to fight cancer. Both Opdivo and Keytruda are immunotherapies that work by blocking PD-1 and have demonstrated impressive activity in the treatment of head and neck cancer.3,4 Clinical studies are ongoing that combine PD-1 inhibitors with other drugs in order to determine their optimal use in the management of throat cancer.
EGFR Inhibitors: Vectibix® (panitumumab) inhibits cancer cell growth and survival by targeting the EGFR. Although a clinical study indicated that Vectibix did not improve overall survival compared to chemotherapy alone, a subset analysis of this study indicated that patients with HPV-negative head and neck cancer did experience an ijmprovement in survival with the addition of Vectibix to chemotherapy.9
1 Adelstein DJ, Tan EH, Lavertu P: Treatment of head and neck cancer: the role of chemotherapy. Crit Rev Oncol Hematol 24 (2): 97-116, 1996.
2 Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992.
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 Bristol-Myers Squibb. First Presentation of Overall Survival Data for Opdivo® (nivolumab) Shows Significant Survival Benefit at One-Year Versus Investigator’s Choice in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck. Available at: http://news.bms.com/press-release/aacr/first-presentation-overall-survival-data-opdivo-nivolumab-shows-significant-survi. Accessed May 1, 2016.
5 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.
6 Vermorken JB, Stohlmacher-Williams J, Davidenko I, et al. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. The Lancet Oncology. 2013; 14(8): 697-710.
7 Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007.
8 US Food and Drug Administration. Cetuximab (Erbitux). November 7, 2011.
- Vermorken J, Stöhlmacher J, Oliner K, et al: Safety and efficacy of panitumumab in HPV positive and HPV negative recurrent/metastatic squamous cell carcinoma of the head and neck: Analysis of the phase 3 SPECTRUM trial. 2011 European Multidisciplinary Cancer Congress. Abstract 25LBA. Presented September 24, 2011.