Single-Agent Pembrolizumab Yields High Response Rates in Patients With Cutaneous Squamous Cell Carcinoma (2023)

By Alice Goodman
May 25, 2021


Single-Agent Pembrolizumab Yields High Response Rates in Patients With Cutaneous Squamous Cell Carcinoma (1)

Single-agent pembrolizumab achieved durable responses and promising survival in patients with locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma, according to the second interim analysis of the phase II ­KEYNOTE-629 study, which was presented at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.1

Objective response rates were 50% for locally advanced cutaneous squamous cell carcinoma and 35.2% for recurrent and/or metastatic cutaneous squamous cell carcinoma. Disease control rates (defined as stable disease for 12 weeks or more plus objective response rates) were 64.8% in the cohort with locally advanced disease and 52.4% in the cohort with recurrent/metastatic disease.

‘Robust, Durable Activity’

(Video) Cutaneous Squamous Cell Carcinoma - Updates in Immunotherapy presented by Dr. Butler MD

“Pembrolizumab has demonstrated robust, durable antitumor activity and promising survival rates in both the locally advanced and recurrent metastatic cutaneous squamous cell carcinoma cohorts,” said lead author Brett G.M. Hughes, MD, of Royal Brisbane and Women’s Hospital, Queensland, Australia. “These data establish pembrolizumab as a promising treatment option for those with locally advanced, recurrent/metastatic cutaneous squamous cell carcinoma.”

“Cutaneous squamous cell carcinoma is the second most common nonmelanoma skin cancer in the world, representing about 20% of all nonmelanoma skin cancers and 20% of all skin cancer–related mortalities,” Dr. Hughes told listeners.

Single-Agent Pembrolizumab Yields High Response Rates in Patients With Cutaneous Squamous Cell Carcinoma (2)

Pembrolizumab has demonstrated robust durable antitumor activity and promising survival in both the locally advanced and recurrent metastatic cutaneous squamous cell carcinoma cohorts.

— Brett G.M. Hughes, MD

Tweet this quote

“In the first interim analysis of this study, we demonstrated that pembrolizumab monotherapy had clinically meaningful and durable antitumor activity, with a manageable safety profile for recurrent and metastatic disease.” The first interim analysis focused on the cohort with recurrent/metastatic disease at a median follow-up of 11.4 months. The objective response rate was 34.3%, complete response rate was 4%, and disease control rate was 52.4% in that cohort.2

At the AACR meeting, Dr. Hughes reported initial efficacy and safety data from the cohort of patients with locally advanced disease, based on a median follow-up of 13.4 months, as well as updated data from the recurrent/metastatic disease cohort, with median follow-up of 23.8 months.

Study Details

(Video) High Risk Cutaneous Squamous Cell Carcinoma: Recognition and Management

The multicenter, open-label, nonrandomized phase II KEYNOTE-629 study was conducted at 59 sites in 10 countries and had two cohorts: locally advanced cutaneous squamous cell carcinoma (n = 54) and recurrent/metastatic cutaneous squamous cell carcinoma (n = 105). All patients were treated with pembrolizumab at 200 mg once every 3 weeks for up to 35 cycles (approximately 2 years) or until protocol-specified treatment discontinuation criteria were met.

Patients eligible for the trial were 18 years or older, had histologically confirmed cutaneous squamous cell carcinoma with measurable disease per Response Evaluation Criteria in Solid Tumors ­(RECIST) version 1.1 by blinded independent central review, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate organ function. Patients in the recurrent/metastatic disease cohort had to have received prior systemic therapy.

In the locally advanced cohort with unresectable disease, 54 patients were enrolled and 30 discontinued therapy. In the recurrent/metastatic disease cohort, 105 patients enrolled and 83 discontinued therapy. Objective response rate per RECIST version 1.1 by blinded review was the primary endpoint of the study. Secondary endpoints included duration of response, disease control rate, progression-free survival, overall survival, and safety/tolerability.

At baseline, the median age of patients was 74 years. The majority of patients were male (74.8%) and had an ECOG performance status of 1 (63.5%).

“In the locally advanced cohort, most patients had a PD-L1 combined proportion score of more than 1%, and 22% of the 54 patients were treated with prior systemic therapy with curative intent. Most commonly, this was platinum-based chemotherapy with radiation,” Dr. Hughes said.

“In the recurrent/metastatic cohort, 91 of the 105, or 86.7%, received prior systemic therapy. After a protocol modification, a small number of patients received treatment as their first line of therapy for recurrent/metastatic disease,” Dr. Hughes noted.

The median time from the first dose to data cutoff on July 29, 2020, was 14.9 months for the locally advanced disease cohort and 27.2 months for the recurrent/metastatic disease cohort.

(Video) Innovative Immunotherapy in Advanced Basal Cell Carcinoma

  • In KEYNOTE-629, single-agent pembrolizumab achieved deep and durable responses as well as promising progression-free survival and overall survival in patients with locally advanced cutaneous squamous cell carcinoma and recurrent and/or metastatic cutaneous squamous cell carcinoma.
  • These results provide convincing data for the use of single-agent pembrolizumab in these settings.

Subgroup Analyses

In a subgroup analysis of objective response rate, overall response was generally consistent across most subgroups analyzed in both cohorts. In the recurrent/metastatic disease cohort, there was a slightly higher response rate observed in patients who received pembrolizumab as first-line therapy: approximately 50% vs 33% for those with prior treatment. Although responses were observed regardless of PD-L1 expression, an increase in objective response was observed among those who had a combined proportion score of 1 or greater or a tumor proportion score of more than 50%.

In the locally advanced and recurrent/metastatic disease cohorts, 9 patients (16.7%) and 11 patients (10.5%), respectively, had a complete response. A partial response was observed in 18 (33.3%) and 26 (24.8%), respectively; stable disease was observed in 13 (24.1%) and 30 (28.6%), respectively; and stable disease for 12 weeks or more was seen in 8 (14.8%) and 18 (17.1%), respectively. Progressive disease was observed in 9 (16.7%) and 28 (26.7%), respectively.

In the overall study population, 20 patients (12.6%) experienced a complete response, 44 (27.7%) had a partial response, 43 (27.0%) had stable disease, 26 (16.4%) had stable disease for 12 weeks or more, and 37 (23.3%) had progressive disease.

“Most responses were deep and significant in the locally advanced disease cohort,” Dr. Hughes said. “Notably, for the first two interim analyses, despite similar overall response and disease control rates, seven patients went from partial response to complete response.”

The 12-month progression-free survival rates in the locally advanced and recurrent/metastatic cohorts were 54% and 36.4%, respectively. Median progression-free survival was not reached in the locally advanced disease cohort and was 5.7 months in the recurrent/metastatic disease group.

(Video) Cutaneous Squamous Cell Carcinoma: What Is Immunotherapy?

The 12-month overall survival rates in the locally advanced and recurrent/metastatic disease cohorts were 73.6% and 61.0%, respectively. Median overall survival was not reached in the group with locally advanced disease and was 23.8 months in those with recurrent/metastatic disease.

Any-grade treatment-related adverse events occurred in 69.2% of patients, including grades 3 to 5 in 11.9% of patients. Treatment-related adverse events led to treatment discontinuation in 8.8% of patients and death in 1.3% of patients. The most common treatment-related adverse events of any grade were pruritus (18.2%), fatigue (14.5%), asthenia (12.6%), rash (10.7%), diarrhea (9.4%), hypothyroidism (8.8%), arthralgia (6.3%), and nausea (5.7%).

DISCLOSURE: Dr. Hughes has served as a consultant or advisor to AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eisai, MSD Oncology, Pfizer, Roche, and Sanofi/Regeneron; has received institutional research funding from Amgen; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca and Bristol Myers Squibb.


1. Hughes BG, Munoz-Couselo E, Mortier L, et al: Phase 2 study of pembrolizumab for locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma: KEYNOTE-629. AACR Annual Meeting 2021. Abstract CT006. Presented April 10, 2021.

2. Grob JJ, Gonzalez R, Basset-Seguin N, et al: Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase II trial ­(KEYNOTE-629). J Clin Oncol 38:2916-2925, 2020.

Expert Point of View: Stefania Scala, MD

Formal discussant Stefania Scala, MD, of the Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, was impressed by the findings of KEYNOTE-629. “The second interim analysis for the locally advanced disease cohort and updated data for the recurrent/metastatic disease cohort of KEYNOTE-629 had ...

(Video) Squamous Cell Carcinoma: What Patients Need to Know


Does Keytruda work on squamous cell carcinoma? ›

KEYTRUDA is a prescription medicine used to treat a kind of skin cancer called cutaneous squamous cell carcinoma (cSCC). KEYTRUDA may be used when your skin cancer has returned or spread, and cannot be cured by surgery or radiation.

How successful is immunotherapy for squamous cell carcinoma? ›

Ratner, cemiplimab is one of the first immunotherapeutic drug available to treat advanced squamous cell carcinoma disease effectively, with response rates of approximately 50%.

What is cutaneous squamous cell carcinoma? ›

(kyoo-TAY-nee-us SKWAY-mus sel KAR-sih-NOH-muh) Cancer that begins in cells that form the epidermis (outer layer of the skin). It usually occurs on areas of the skin that have been exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.

Can immunotherapy help squamous cell carcinoma? ›

Immunotherapy is the use of medicines to stimulate a person's own immune system to recognize and destroy cancer cells more effectively. It can be used to treat some people with advanced basal or squamous cell skin cancer.

What is the best treatment for squamous cell carcinoma in situ? ›

Mohs surgery is the most effective technique for removing SCCs, sparing the greatest amount of healthy tissue while achieving the highest possible cure rate – up to 97 percent for tumors treated for the first time.

What is the best treatment for squamous cell carcinoma stage 2? ›

However, if it's caught at stage 2, treatments for the disease are often quite successful. Some of the most effective treatment options may include surgical removal of the tumor (including Mohs surgery), curettage and electrodessication, and other therapies like radiation or chemotherapy.

Which squamous cell carcinoma has best prognosis? ›

Patients with stage I, II, or III cancer have the best survival, whereas patients with stage IV or recurrent cancer who are older than 66.5 years have the worst survival. Patients with stage IV or recurrent cancer who are younger than 66.5 years have intermediate survival.

Can squamous cell carcinoma be completely cured? ›

Most squamous cell skin cancers are found and treated at an early stage, when they can be removed or destroyed with local treatment methods. Small squamous cell cancers can usually be cured with these treatments.

How is cutaneous squamous cell carcinoma treated? ›

Options might include:
  1. Simple excision. In this procedure, your doctor cuts out the cancerous tissue and a surrounding margin of healthy skin. ...
  2. Mohs surgery. During Mohs surgery, your doctor removes the cancer layer by layer, examining each layer under the microscope until no abnormal cells remain. ...
  3. Radiation therapy.
13 May 2021

Is cutaneous squamous cell carcinoma rare? ›

Cutaneous squamous cell carcinoma (CSCC, also called squamous cell carcinoma of the skin) is the second most common form of skin cancer and five times more prevalent than melanoma in the U.S.1-3 That adds up to an estimated 1.8 million cases diagnosed every year – or 205 cases every hour.

Can cutaneous carcinoma be cured? ›

Nearly all skin cancers can be cured if found and treated early. Treatments include excision, cryotherapy, Mohs surgery, chemotherapy and radiation. Check your skin for any changes in size, shape or color of skin growths. See your dermatologist once a year for a professional skin checkup.

What is the best chemo for squamous cell carcinoma? ›

If squamous cell carcinoma has spread, chemo might be an option, although an immunotherapy drug might be used first. If chemo is used, drugs such as cisplatin and 5-fluorouracil (5-FU) might be options. These drugs are given into a vein (intravenously, or IV), usually once every few weeks.

Can squamous cell carcinoma go into remission? ›

A phase II clinical trial of cetuximab as first-line therapy in patients with unresectable SCC of the skin found 58% of patients achieved stable disease [10]. Only 8% had a partial response and 3% (one patient) had complete remission.

Can you beat stage 4 squamous cell carcinoma? ›

At stage 4 your cancer may not be curable, but it is still treatable.

What is the difference between squamous cell carcinoma and squamous cell carcinoma in situ? ›

Squamous cell carcinoma in situ, also called Bowen disease, is the earliest form of squamous cell skin cancer. “In situ” means that the cells of these cancers are still only in the epidermis (the upper layer of the skin) and have not invaded into deeper layers.

Is Mohs surgery necessary for squamous cell carcinoma in situ? ›

Mohs surgery is the gold standard for treating many basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), including those in cosmetically and functionally important areas around the eyes, nose, lips, ears, scalp, fingers, toes or genitals.

Who should treat squamous cell carcinoma? ›

Most basal and squamous cell cancers (as well as pre-cancers) are treated by dermatologists – doctors who specialize in treating skin diseases. If the cancer is more advanced, you may be treated by another type of doctor, such as: A surgical oncologist: a doctor who treats cancer with surgery.

Is squamous cell carcinoma Stage 3 curable? ›

Squamous cell carcinoma is considered curable when caught early. Stage 3 skin cancer has spread to nearby tissues and lymph nodes and, thus, is more difficult to treat. This type of cancer is treatable with surgery and other treatment options, like chemotherapy and radiation therapy.

How do you shrink squamous cell carcinoma? ›

Cryosurgery: This treatment involves using an extremely cold substance, such as liquid nitrogen, to destroy the cancer cells. Although seldom used to treat SCC, cryotherapy can be an option when the cancer is caught early, or a patient cannot have any type of surgical removal.

Why does squamous cell carcinoma keep coming back? ›

That's because individuals who were diagnosed and treated for a squamous cell skin lesion have an increased risk of developing a second lesion in the same location or a nearby skin area. Most recurrent lesions develop within two years after the completion of treatment to remove or destroy the initial cancer.

What is the life expectancy of someone with squamous cell carcinoma? ›

In general, the squamous cell carcinoma survival rate is very high—when detected early, the five-year survival rate is 99 percent. Even if squamous cell carcinoma has spread to nearby lymph nodes, the cancer may be effectively treated through a combination of surgery and radiation treatment.

Is squamous cell carcinoma ever fatal? ›

Untreated squamous cell carcinoma of the skin can destroy nearby healthy tissue, spread to the lymph nodes or other organs, and may be fatal, although this is uncommon.

What percentage of squamous cell carcinoma cases can metastasis? ›

Metastasis of cutaneous squamous cell carcinoma (cSCC) is rare. However, certain tumor and patient characteristics increase the risk of metastasis. Prior studies have demonstrated metastasis rates of 3-9%, occurring, on average, one to two years after initial diagnosis [6].

Can you live a long life with squamous cell carcinoma? ›

Most (95% to 98%) of squamous cell carcinomas can be cured if they are treated early. Once squamous cell carcinoma has spread beyond the skin, though, less than half of people live five years, even with aggressive treatment.

How do you prevent squamous cell carcinoma from coming back? ›

Preventing Squamous Cell Carcinoma of the Skin
  1. Checking your skin once a month.
  2. Seeing a dermatologist annually.
  3. Using sunscreen. To be effective, sunscreens should be broad spectrum, at least SPF 30 and waterproof. ...
  4. Avoid tanning beds.
  5. Wearing protective clothing.

Does squamous cell carcinoma always spread? ›

Although squamous cell carcinoma can be more aggressive than basal cell cancer, the risk of this type of cancer spreading is low—as long as the cancer is treated early, Dr. Leffell says.

Is cutaneous squamous cell carcinoma melanoma? ›

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form.

Is cutaneous squamous cell carcinoma painful? ›

Itch was the most common symptom reported in both skin cancers - 43.5 percent of SCCs and 33.4 percent of BCCs, but the prevalence of pain was significantly increased in SCC (39.8 percent) as compared to BCC (17.7 percent).

Should I worry if I have squamous cell carcinoma? ›

They are of concern because of the similarity to squamous cell cancer. Squamous cell carcinoma is one of the three most common types of skin cancer. Basal cell, squamous cell, and melanoma. Squamous cell cancers can metastasize (spread) and should be removed surgically as soon as they are diagnosed.

What do the majority of cutaneous squamous cell carcinoma deaths result from? ›

Cutaneous squamous cell carcinoma (SCC) in white populations is caused predominantly by sun (ultraviolet radiation, UV) exposure. Carcinogenesis is due to UV-induced DNA damage in keratinocytes lacking sufficient melanin protection.

Can squamous cell carcinoma spread to the brain? ›

Squamous cell carcinomas are defined as relatively slow-growing malignant (cancerous) tumors that can spread (metastasize) to surrounding tissue if left untreated. Squamous cell carcinoma may spread to the sinuses or skull base, or other areas of the brain.

What happens if squamous cell carcinoma spreads to lymph nodes? ›

When squamous cell cancer spreads to lymph nodes in the neck or around the collarbone, it is called metastatic squamous neck cancer. The doctor will try to find the primary tumor (the cancer that first formed in the body), because treatment for metastatic cancer is the same as treatment for the primary tumor.

Which is the considered highest risk site in squamous cell carcinoma? ›

The sun-exposed head and neck are the most frequent sites for these cancers to arise and in most patients diagnosed with a cutaneous squamous cell carcinoma, local treatment is usually curative. However, a subset is diagnosed with a high-risk cutaneous squamous cell carcinoma.

What is considered high-risk squamous cell carcinoma? ›

"High-risk" cSCCs are tumors that exhibit clinical or histologic features that have been associated with increased risk for aggressive tumor behavior. The best approach to the management of high-risk cSCC is not definitively known.

What kills squamous cell carcinoma? ›

Chemotherapy. Chemotherapy uses powerful drugs to kill cancer cells. If squamous cell carcinoma spreads to the lymph nodes or other parts of the body, chemotherapy can be used alone or in combination with other treatments, such as targeted drug therapy and radiation therapy.

What cancers are approved for Keytruda? ›

Keytruda is used alone or with other drugs to treat certain types of breast cancer, skin cancer (squamous cell carcinoma of the skin, Merkel cell carcinoma, and melanoma), colorectal cancer, endometrial cancer, renal cell carcinoma (a type of kidney cancer), esophageal cancer, gastroesophageal junction cancer, stomach ...

How often is squamous cell carcinoma fatal? ›

In general, the squamous cell carcinoma survival rate is very high—when detected early, the five-year survival rate is 99 percent. Even if squamous cell carcinoma has spread to nearby lymph nodes, the cancer may be effectively treated through a combination of surgery and radiation treatment.

What foods fight squamous cell carcinoma? ›

Food That Lower Your Skin Cancer Risk

Vitamin C – Citrus fruits, strawberries, raspberries, broccoli, bell peppers, and leafy greens. Vitamin D and Omega-3 fatty acids – Fatty fish, like mackerel, sardines, herring, tuna, and salmon. Vitamin D – Milk, cheese, and vitamin D-fortified orange juice.

What is the success rate of Pembrolizumab? ›

Of the patients who completed approximately two years of treatment (35 cycles) with KEYTRUDA plus pemetrexed and cisplatin or carboplatin (n=57/405), 71.9% were alive at five years following randomization, with an ORR of 86.0% (with eight complete responses and 41 partial responses).

What is the success rate of KEYTRUDA? ›

Half (50%) of the patients who received Keytruda every 3 weeks were alive at 4.1 months, compared to 2.8 months for patients receiving Yervoy. Keytruda was shown to reduce the risk of dying by 31% compared to Yervoy.

When should you not take KEYTRUDA? ›

Conditions: overactive thyroid gland. a condition with low thyroid hormone levels. myasthenia gravis, a skeletal muscle disorder.


1. Cutaneous Melanoma Surgical Treatment 2022 Update
(Ventura Surgery School)
2. NCCN Patient Webinar: Basal Cell Skin Cancer
3. Targeting TIGIT to Extend Immunotherapy Benefits to More Cancer Patients
(PeerView Oncology)
4. Immunotherapy in Non-Small Cell Lung Cancer (NSCLC): Front Line Therapy
(HMP Education)
5. Advanced Squamous NSCLC: The IMpower131 Study
6. Melanoma and the Immune Response
Top Articles
Latest Posts
Article information

Author: Lilliana Bartoletti

Last Updated: 01/08/2023

Views: 6599

Rating: 4.2 / 5 (73 voted)

Reviews: 88% of readers found this page helpful

Author information

Name: Lilliana Bartoletti

Birthday: 1999-11-18

Address: 58866 Tricia Spurs, North Melvinberg, HI 91346-3774

Phone: +50616620367928

Job: Real-Estate Liaison

Hobby: Graffiti, Astronomy, Handball, Magic, Origami, Fashion, Foreign language learning

Introduction: My name is Lilliana Bartoletti, I am a adventurous, pleasant, shiny, beautiful, handsome, zealous, tasty person who loves writing and wants to share my knowledge and understanding with you.