Tag: Non-Melanomatous Skin Cancers

FDA Approves LIBTAYO® for Advanced Basal Cell Carcinoma

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SUMMARY: The FDA on February 9, 2021, granted regular approval to LIBTAYO® (Cemiplimab-rwlc) for patients with locally advanced Basal Cell Carcinoma (laBCC) previously treated with a HedgeHog pathway Inhibitor (HHI) or for whom a HHI is not appropriate, and granted accelerated approval to LIBTAYO® for patients with metastatic BCC (mBCC) previously treated with a HHI or for whom a HHI is not appropriate.

BCC is the most common type of skin cancer in the U.S., with approximately two million new cases diagnosed every year. Exposure to UltraViolet rays is a significant risk factor. Majority of BCCs are diagnosed early and cured with surgery and radiation. However, a small proportion of tumors can become locally advanced or progress to metastatic disease and can be painful and disfiguring. The primary systemic treatment options for these patients with advanced BCC are oral HedgeHog pathway inhibitors such as ERIVEDGE® (Vismodegib) and ODOMZO® (Sonidegib). There are however no FDA-approved treatment options available, for patients who progress on, or are intolerant to HedgeHog Inhibitors (HHIs).

LIBTAYO® is a fully human IgG4, high affinity anti-PD-1, monoclonal antibody, that binds to the PD-1 receptor on tumor-infiltrating T cells and blocks its interaction with tumor derived ligands PD-L1 and PD-L2, thereby undoing PD-1 pathway-mediated inhibition of the immune response and unleashing the tumor-specific effector T cells. LIBTAYO® was previously approved by the FDA in 2018 as the first systemic treatment for adults with metastatic Cutaneous Squamous Cell Carcinoma (CSCC) or locally advanced CSCC, who are not candidates for curative surgery or curative radiation.

The present FDA approval of LIBTAYO® was based on results from an interim analysis of an ongoing open-label, multi-center, non-randomized Phase II trial (Study 1620), involving patients with unresectable locally advanced BCC or metastatic BCC (nodal or distant). This was the first and largest prospective clinical trial (N=132) among this patient population, with 112 patients included in the efficacy analysis. Patients in both cohorts (locally advanced and metastatic) had either progressed on HHI therapy, had not had an objective response after 9 months on HHI therapy, or were intolerant of prior HHI therapy. Eligibility required that locally advanced BCC patients were not candidates for curative surgery or curative RT, per multidisciplinary assessment. All patients received LIBTAYO® 350 mg IV over 30 minutes every 3 weeks for up to 93 weeks, until disease progression, unacceptable toxicity, or completion of planned treatment. No PD-L1 or Tumor Mutational Burden (TMB) testing was required before starting treatment with LIBTAYO®. The Primary efficacy endpoint was confirmed Objective Response Rate (ORR) and a key Secondary endpoint was Duration of Response (DOR), as assessed by Independent Central Review.

Among the 84 patients with locally advanced BCC, the confirmed ORR was 29% with a median DOR not reached, and 79% of responders maintained their response for at least 6 months. Among 28 patients with metastatic BCC, the confirmed ORR was 21%, with a median DOR not reached, and all responders maintained their responses for at least 6 months. The most common adverse reactions (incidence 20% or more) were fatigue, musculoskeletal pain, diarrhea, rash, and pruritis.

It was concluded from this study that LIBTAYO® is the first agent to provide clinically meaningful anti-tumor activity including durable responses, in patients with advanced BCC, after progression or intolerance on HHI therapy.

Interim Analysis of Phase 2 Results for Cemiplimab in Patients with Metastatic Basal Cell Carcinoma (mBCC) who Progressed on or are Intolerant to Hedgehog Inhibitors (HHIs). Lewis KD, Peris K, Sekulic A, et al. Presented at the 2021 Winter Clinical Dermatology Conference, January 16–24, Virtual Conference (encore of SITC 2020 poster presentation).

LIBTAYO® (Cemiplimab-rwlc)

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The FDA on February 9, 2021 granted regular approval to LIBTAYO® for patients with Locally Advanced Basal Cell Carcinoma (laBCC) previously treated with a HedgeHog pathway Inhibitor (HHI) or for whom a HHI is not appropriate, and granted accelerated approval to LIBTAYO® for patients with metastatic BCC (mBCC) previously treated with a HHI or for whom a HHI is not appropriate. LIBTAYO® is a product of Regeneron Pharmaceuticals, Inc.

American Society of Clinical Oncology Policy Statement on Skin Cancer Prevention

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SUMMARY: Skin Cancer is the most common cancer diagnosed in the US and around the world. Basal Cell Carcinoma (BCC) and Squamous Cell Carcinoma (SCC) are the two most common types of skin cancers. It is estimated that 5.4 million cases of BCC and SCC are diagnosed each year in the US (occurring in about 3.3 million Americans, as some individuals have more than one type of skin cancer), and 8 of 10 are BCCs, whereas SCCs occur less often. Although the overall mortality rate from these cancers are low, SCCs are almost exclusively responsible for approximately 3,000 deaths per year in the US, with the greatest mortality risk among transplant recipients, who are immunocompromised. Malignant Melanoma of the skin occurs less frequently than BCC and SCC, and the American Cancer Society estimates that in the US for 2020, about 100,350 new melanomas will be diagnosed and about 6,850 people are expected to die of the disease. The rates of skin cancer have been rising rapidly over the past several years, with the economic cost estimates of $8.1 billion annually in the US.

Exposure to UltraViolet (UV) rays is a major risk factor for most skin cancers. Sunlight is the main source of UV rays. UV rays-emitting indoor tanning devices such as tanning beds, sunlamps, and UV lamps, are another source of UV rays. The risk of UV rays associated skin cancers, particularly for SCC, is dose dependent, and increases with greater duration and intensity of exposure. This risk is increased with cumulative solar UV rays exposure over an individual’s lifetime. For a given level of UV rays exposure, skin cancer risk is highest among UV ray sensitive phenotypes who typically are fair skinned, and have a propensity to sunburn, blister and/or freckle, upon exposure to UV rays. National surveys on sun exposure in the US illustrate the high rates of sunburn among adults (35%) and high school students (57%), emphasizing the importance of primary and secondary prevention strategies in the younger population. The ASCO’s 2019 National Cancer Opinion Survey found that only 49% of respondents reported using sunscreen to prevent skin cancer. Skin cancer is less common in individuals with darker skin colors (Black and Latino individuals), due to greater levels of melanin in the skin, which inherently has photoprotective ability. Nonetheless, when skin cancers do occur in individuals with darker skin tones, they tend to be more aggressive, possibly due to delayed diagnosis, as these individuals may be less aware of their skin cancer risks.

Given that skin cancer has such a major impact on society, the American Society of Clinical Oncology (ASCO) earlier this year published a policy statement aimed at lessening the burden of skin cancer through reducing exposure to UV radiation for youth and adults. This policy statement included a review of the risk factors for skin cancer, disparities in incidence, diagnosis and survival among different populations, and public health strategies for Primary and Secondary skin cancer prevention.

ASCO presented recommendations across the following four themes:

Reduce Exposure to Indoor Tanning
1) A major opportunity to prevent skin cancer is by reducing UV ray exposure through avoidance of indoor tanning.
2) Avoidance of indoor tanning holds particular promise in influencing adolescents and sexual minority men because of their higher rate of exposure to tanning.
3) The International Agency for Research on Cancer concluded that UV ray-emitting indoor tanning devices were carcinogens and there is now high-quality scientific evidence documenting strong and consistent associations between indoor tanning devices and skin cancer risk.
4) Indoor tanning is higher among non-Hispanic white females compared with all other population subgroups, and its direct association with melanoma risk likely explains the higher melanoma incidence in this group compared with male adolescents and young adults.
5) There is evidence suggesting the presence of “tanning dependence”, similar to substance use dependence, among individuals who engage in indoor tanning.
6) Recognizing that indoor tanning devices are a threat to public health, several cancer care and public health organizations support strong restrictions designed to prevent the use of UV ray-emitting tanning devices. ASCO supports strengthened laws and regulations restricting such products

Increase Public Efforts to Promote Sun Protection
1) Local, state, and federal laws should support policies that allow students to carry and use sunscreen products without physician authorization.
2) Enhance the protection of young people by encouraging the increased use of broad-spectrum sunscreen and protective clothing, through educational programs.
3) Improvement in sunscreen products and public education to prevent intentional sun exposure, for promoting Vitamin D synthesis.
4) Private and public institutions should be encouraged in their efforts to create more shaded areas in places used for outdoor recreation.
5) Development of new educational efforts, to change the social perceptions of tanned skin.

Community Education and Outreach
1) Investing in prevention research, and continued support for the National Cancer Institute’s Division of Cancer Prevention and the Centers for Disease Control and Prevention’s National Skin Cancer Prevention Education Program, to address the burden of this disease among persons of color, lower socioeconomic status populations, and sexual minorities.
2) ASCO and the cancer care community should work together to develop effective methods for outreach and health communication, to the diverse segments of the population at risk of skin cancer.

Role of Oncology Providers
1) Research has shown that cancer survivors do not adhere to skin-protective behaviors, anymore than the lay public who have not been diagnosed with cancer.
2) Oncologists should discuss with their patients the regular use of properly applied broad-spectrum sunscreen and the use of sun-protective clothing such as hats, long sleeves, and long pants when outdoors, as well as avoidance of UV rays either from sunlight, or from UV ray-emitting indoor tanning devices.
3) Oncology providers should be vocal supporters of skin cancer prevention policies and should educate patients of color, so that they understand that they are also at risk of skin cancer.

American Society of Clinical Oncology Policy Statement on Skin Cancer Prevention. Alberg AJ, LoConte NK, Foxhall L, et al. JCO Oncology Practice. 2020;16:490-499.

LIBTAYO® (Cemiplimab-rwlc)

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The FDA on September 28, 2018 approved LIBTAYO® for patients with metastatic Cutaneous Squamous Cell Carcinoma (CSCC) or locally advanced CSCC, who are not candidates for curative surgery or curative radiation. LIBTAYO® is a product of Regeneron Pharmaceuticals Inc.

ODOMZO® (Sonidegib)

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The FDA on July 24, 2015 approved ODOMZO® for the treatment of patients with locally advanced Basal Cell Carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. ODOMZO® capsules are a product of Novartis Pharmaceuticals Corporation

Nicotinamide Reduces the Incidence of Non-Melanomatous Skin Cancers

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SUMMARY: Skin cancer is the most common of all cancers. Approximately, 3.5 million cases of Basal cell and Squamous cell skin cancer (Non-Melanomatous) are diagnosed in the US each year. Most Non-Melanomatous skin cancers develop on the sun-exposed areas of the skin and Basal cell cancers tend to be slow growing and rarely metastasize, whereas Squamous cell cancers are more likely to grow into deeper layers of skin and metastasize. There has been a 35% increase in the incidence of Non-Melanomatous skin cancers between 2006 and 2012 and there has been a 17% increase in the incidence of Basal cell carcinomas over the past 15 years. Patients with Non-Melanomatous skin cancer are at an increased risk of developing a new primary, including breast and lung cancer in woman and prostate cancer in men. A major risk factor for most skin cancers is exposure to UltraViolet (UV) radiation, which damages the DNA of skin cells and suppresses cutaneous immunity. The main source of UV rays are sunlight, tanning lamps and tanning beds. The 3 main types of UV rays include UVA rays, UVB rays that mainly cause sunburns and UVC rays that do not penetrate through our atmosphere and are not in sunlight. Most indoor tanning beds give off large amounts of UVA rays, which have been found to increase skin cancer risk. It appears that there are no safe UV rays. Nicotinamide is an amide form of Vitamin B3 and unlike Nicotinic acid does not cause vasodilatation and associated side effects. Severe Nicotinamide deficiency causes Pellagra, which is characterized by photosensitive dermatitis, dementia, diarrhea and death. Nicotinamide enhances DNA repair after UV exposure and reduces UV radiation induced immunosuppression and in previously published studies was shown to decrease the formation of Actinic keratoses.

The ONTRAC (Oral Nicotinamide to Reduce Actinic Cancer) trial is a double-blind, phase III Study, in which 386 patients were randomly assigned to receive either Nicotinamide 500 mg PO twice daily (N=193 patients) or placebo (N=193 patients), for a period of 12 months. Enrolled patients had 2 or more histologically confirmed Non-Melanomatous skin cancers during the previous 5 years. The mean age was 66 years and 63% of the enrollees were men. Skin evaluations were performed by Dermatologists every 3 months. The primary endpoint was the number of new Non-Melanomatous skin cancers at 12 months and secondary endpoints included number of Squamous cell carcinomas, Basal cell carcinomas, and Actinic keratoses over the same study period. Over the 12 month study period, it was noted that patients in the placebo group developed an average of 2.4 new Non-Melanomatous skin cancers compared with 1.8 in the Nicotinamide group. This meant a Relative Risk Reduction (RRR) of 0.23 (P= 0.02). With regards to the specific subtypes, there was an average of 1.7 new cases of Basal cell carcinoma for patients who received placebo compared to 1.3 new cases for patients who received Nicotinamide. The Relative Risk Reduction was 0.20 (P=0.1). For Squamous cell carcinomas, there was an average of 0.7 cases for patients in the placebo group compared with 0.5 in the Nicotinamide group. The Relative Risk Reduction was 0.30 (P= 0.05). With regards to Actinic keratosis, there was a Relative Risk Reduction of 11% at 3 months (P=0.01), 14% at 6 months (P<0.001), 20% at 9 months (P<0.0001) and 13% at 12 months (P<0.005).

Based on this data the authors concluded that Nicotinamide, an inexpensive, over-the-counter Vitamin supplement, significantly reduces the incidence of Non-Melanomatous skin cancers by 20-30%, in high risk patients and may be an effective chemopreventive agent for Non-Melanomatous skin cancers. Oral nicotinamide to reduce actinic cancer: A phase 3 double-blind randomized controlled trial. Martin AJ, Chen A, Choy B, et al. J Clin Oncol 33, 2015 (suppl; abstr 9000)

ERIVEDGE® (Vismodegib)

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The FDA on January 30, 2012 approved ERIVEDGE® for the treatment of adults with metastatic basal cell carcinoma or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. ERIVEDGE® is a product of Genentech, Inc.