Amid the encouraging studies reported at the 2015 ASCO Annual Meeting about advances in the treatment of melanoma was a troubling finding about the incidence of melanoma increasing. An analysis of data from nine Surveillance, Epidemiology, and End Results (SEER) registries found that the incidence of melanoma in children, adolescents, and young adults increased 253% between 1973 and 2011.1
Just as the Annual Meeting was ending, the Centers for Disease Control and Prevention (CDC) released a Vital Signs report noting that the rate of new cases of melanoma had doubled, from 11.2 to 22.7 per 100,000 between 1982 and 2011. Without additional prevention efforts, the CDC predicted, that rate will continue to increase, with 112,000 new cases projected in 2030.2,3
Among the efforts urged by the CDC to prevent melanoma is education about protecting the skin from exposure to ultraviolet radiation. And it seems the public is particularly interested in information on skin cancer in the summer months.
Indeed, a Research Letter in JAMA Dermatology reported that Google searches for information about skin cancer “increased during each summer yearly but have remained stable for 5 years (2010–2104). Searches for melanoma mirrored the search volume for skin cancer.”4 The authors concluded: “Because the U.S. population seeks information regarding skin cancer at a greater level during the summer months, this might be the most efficient time for educational and public health initiatives.”
Time of Year to Raise Awareness
In an interview with The ASCO Post, Lynn M. Schuchter, MD, said, “We definitely take advantage of this time of year to raise awareness about skin cancer and melanoma.” Dr. Schuchter is the University of Pennsylvania Willard Robinson Professor of Hematology/Oncology, Chief of the Hematology/Oncology Division, and Program Leader for the Abramson Cancer Center’s National Cancer Institute approved and funded Melanoma Research Program. She is also Scientfic Program Leader for the ASCO Annual Meeting in 2016 and served as an ASCO expert at this year’s Annual Meeting.
Dr. Schuchter noted that May is Melanoma Awareness Month, and skin cancer education efforts continue through the summer months. “We do try to capitalize on that,” Dr. Schuchter said. Dermatologists as well as other physicians and health educators work to promote the use of sunscreen products and get people “reeducated on ‘smart sun strategies,’” she added.
“We’re working on communication strategies so that especially young people take in and understand the warning that ultraviolet radiation is a carcinogen,” Dr. Schuchter continued. “People sometimes don’t understand that melanoma is serious. They hear the words ‘skin cancer’ and don’t get too alarmed, but obviously melanoma is a serious skin cancer.”
Restricting Access to Indoor Tanning
The SEER data analysis showing a 253% increased incidence of melanoma among children, adolescents, and young adults found that white female young adults are at particular high risk.1 “There is a lot of concern that the rising increase in young women is partially related to tanning salon use,” Dr. Schuchter said.
The CDC Vital Signs report called on policymakers and members of the community to “restrict the availability and use of indoor tanning by minors.”2 Legislation that would do that—mainly by requiring parental consent for indoor tanning by those under 18 years old—“has been moving more through state legislatures” and is “very difficult to enforce,” Dr. Schuchter noted.
Other legislation being promoted would require that the U.S. Food and Drug Administration label tanning salons as carcinogenic, Dr. Schuchter said. On the regulatory front, efforts include looking very carefully at the advertising for tanning salons to make sure that indoor tanning is not being promoted as a safe way to tan, Dr. Schuchter added. Indoor tanning, she stressed, is not a safe alternative to sun exposure.
Trend Toward Earlier Diagnosis
The SEER data analysis also found a trend in diagnosis at an earlier disease stage.1 Skin cancer screening, however, is not recommended by the U.S. Preventive Services Task Force, which concluded: “the current evidence is insufficient to assess the benefits and harms of using a whole-body skin examination by a primary care clinician or patient skin self-examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer in the adult general population.”5 That statement is in the process of being updated.
There is no recommendation because there hasn’t been a study showing mortality data related to screening, Dr. Schuchter said. “But there are definitely groups of people who would benefit from skin examinations. Those who have had a personal history of melanoma, family history of melanoma, or other nonmelanoma skin cancers and individuals with dysplastic nevi should be screened,” she explained.
There are tools to calculate melanoma risk, Dr. Schuchter noted. “There is the Fears model that we have developed, where you can quickly—just by looking at someone’s back and asking a few questions—identify, from a primary care perspective, whether a patient should be referred to a dermatologist,” Dr. Schuchter reported. These questions are aimed at determining a patient’s age, race, and gender and whether the patient lives in the northern, southern, or central United States.
This melanoma risk calculation tool was developed using data from a case control study that included 718 non-Hispanic white patients with invasive cutaneous melanoma and 945 matched controls.6 The tool is not recommended for use with other races or ethnicities.
When screening is recommended because of a high risk for melanoma, it is usually on an annual basis, although sometimes more frequent exams are called for. “There is a group of patients who have atypical nevi or dysplastic nevi who may have skin exams twice a year,” Dr. Schuchter noted.
Other ASCO 2015 Melanoma Studies
The melanoma study presented at ASCO 2015 probably receiving the most media attention was the CheckMate 067 trial finding that for patients with previously untreated advanced melanoma, initial treatment with nivolumab (Opdivo) improved progression-free survival compared to ipilimumab (Yervoy), but the benefit was greater when the two agents were used together.7 “That study combined with other recent data shows the importance of checkpoint blockade in treating melanoma. There is no question about that. This approach is highly effective,” Dr. Schuchter stated.
“But I don’t think it is clear that we should be using combination ipilimumab and nivolumab as the new standard of care if you are using immunotherapy,” she continued. “As single agents, nivolumab and pembrolizumab (Keytruda) are very active, and [CheckMate 067] wasn’t powered to tell the difference between single-agent nivolumab and the combination. I think we need to wait for longer follow-up and survival data before saying that combination therapy is the first choice, because of the toxicity issue. There is no question that when you combine the two, there is much more significant toxicity.”
Dr Schuchter pointed out that there are other strategies being tested combining targeted therapies with immunotherapies. “It is a rapidly evolving field, and now it is going to be important to look not just at response rate and progression-free survival but at overall survival as well—and to look closely at toxicity,” she stressed.
The authors of a study showing that complete lymph node dissection did not significantly improve survival for patients with melanoma and micrometastases said the results raise questions about general recommendations for complete lymph node dissection in patients with positive nodes, and the authors expect that surgical practice will change.8
“I think that studies like this are potentially practice-changing, saying that maybe we don’t need to do complete lymph node dissection,” Dr. Schuchter said. She noted, however, that there is “a much larger international study being done [Multicentre Selective Lymphadenectomy Trial 2, or MSLT-2)], looking at complete lymph node dissection vs observation with monitoring. I think that is going to be the definitive study. Meanwhile, these are the data we have, and the overall survival was identical, with nearly 500 patients enrolled.” The results of MSLT-2 are not expected until 2022.
“In my own practice, I recommend complete lymph node dissection for most of my patients,” Dr. Schuchter said. “In selected patients, one could consider not proceeding because of the concern about lymphedema.”
She pointed out that adjuvant clinical trials currently require complete surgical staging. Thus, if patients don’t have complete lymph node dissection, they are not eligible for adjuvant clinical trials. She predicted that “eventually we will see clinical trials in the adjuvant setting also change” so that complete lymph node dissection is not a requirement for eligibility.
Updates were also presented at ASCO 2015 on combined BRAF and MEK inhibitors for patients with BRAF-mutant melanoma. “Going forward, most studies are focused on how best to sequence the therapies,” Dr. Schuchter said. “Do you do immunotherapy first or targeted therapy? Should you be doing combination strategies? There is a lot of new research in the area of resistance, both for targeted therapies and immunotherapies—understanding why a patient responds to immunotherapy and then stops, and what are the mechanisms of resistance.”
While the majority of patients with stage IV melanoma “are either not going to respond or will respond and then [have disease progression],” Dr. Schuchter said, “a minority may be cured.” She noted that in 26 years of treating patients with melanoma, “it is the first time I am saying that for stage IV melanoma.” ■
Disclosure: Dr. Schuchter reported no potential conflicts of interest.
References
1. Mitsis DKL, Groman A, Beaupin LM, et al: Trends in demographics, incidence, and survival in children, adolescents, and young adults (AYA) with melanoma: A Surveillance, Epidemiology, and End Results (SEER) population-based analysis. 2015 ASCO Annual Meeting. Abstract 9058. Presented June 1, 2015.
2. Centers for Disease Control and Prevention: Preventing melanoma. Vital Signs, June 2015. Available at cdc.gov/vitalsigns/melanoma. Accessed June 17, 2015.
3. Centers for Disease Control and Prevention: Rates of new melanoma—deadly skin cancers—have doubled over last three decades. Available at cdc.gov/media/releases/2015. Accessed June 17, 2015.
4. Bloom R, Amber KT, Hu S, et al: Google search trends and skin cancer: Evaluating the US population’s interest in skin cancer and its association with melanoma outcomes. JAMA Dermatology. June 10, 2015 (early release online).
5. U.S. Preventive Services Task Force: Skin cancer screening (recommendation statement). Released February 2009. Available at uspreventiveservicestaskforce.org. Accessed June 22, 2015.
6. Fears TR, Guerry D 4th, Pfeiffer RM, et al: Identifying individuals at high risk of melanoma: A practical predictor of absolute risk. J Clin Oncol 24:3590-3596, 2006.
7. Wolchok JD, Chiarion-Sileni V, Gonzales R, et al: Efficacy and safety results from a phase III trial of nivolumab alone or combined with ipilimumab versus ipilimumab alone in treatment-naive patients with advanced melanoma (Checkmate 067). 2015 ASCO Annual Meeting. Abstract LBA1. Presented May 31, 2015.
8. Leiter U, Stadler R, Mauch C, et al: Survival of SLNB-positive melanoma patients with and without complete lymph node dissection: A multicenter, randomized DECOG trial. 2015 ASCO Annual Meeting. Abstract LBA9002. Presented May 30, 2015.
