Metastatic Melanoma: Not Quite Curable…But Getting There


By 2050, the number of deaths due to malignant melanoma in the U.S. could be three times lower than peak levels reached before 1960. Researchers presented the data behind this prediction at the 2017 European Cancer Congress in January.

It is unclear how much of this anticipated decline in deaths can be attributed to the availability of new, effective treatments. However, it is obvious that much-increased awareness of sunlight exposure as the single factor most responsible for the development of skin melanoma has contributed to lower incidence of the disease.

In any case, the armament of treatments available for metastatic melanoma is currently such that this diagnosis has transformed from being almost universally fatal (even just a few years ago) into a being largely treatable. Since 2011, the U.S. Food and Drug Administration (FDA) has approved eight new drugs for melanoma. Continue reading…


Binimetinib Delayed Progression of NRAS-Mutant Melanoma

Excerpt:

“The MEK inhibitor binimetinib improved progression-free survival compared with dacarbazine in patients with NRAS-mutant melanoma, according to the phase III results of the NEMO trial published in Lancet Oncology.

“In addition, improved progression-free survival was seen in patients who had previously failed immunotherapy, the current guideline-recommended first-line treatment.

” ‘Future treatment algorithms for metastatic melanoma might incorporate binimetinib therapy in patients with advanced NRAS-mutant melanoma, including after the failure of immunotherapy,’ wrote Reinhard Dummer, MD, of the department of dermatology at the University Hospital Zurich Skin Cancer Center in Switzerland, and colleagues.”

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Melanoma: New Drugs and New Challenges (Part 2 of 2)


Editor’s note: This is part 2 of a 2-part post on the latest research in melanoma. To learn about research into drug combinations for melanoma that may work better than single drugs, check out Melanoma: New Drugs and New Challenges (Part 1 of 2).

As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…


Lead NEMO Author Shares Excitement With Binimetinib in NRAS-Mutant Melanoma

Excerpt:

“For patients with NRAS-mutant melanoma who progress following treatment with an immunotherapy agent, the MEK inhibitor binimetinib offers a promising option, explains Reinhard Georg Dummer, MD.

“Results of the open-label phase III NEMO trial, which were presented during the 2016 ASCO Annual Meeting,1 most recently demonstrated the agent’s potential. In the study, binimetinib was found to reduce the risk of progression or death by 38% when compared with dacarbazine in this subgroup of patients.

“Additionally, median progression-free survival (PFS) with binimetinib was 2.8 months versus 1.5 months with dacarbazine (HR, 0.62; 95% CI, 0.47-0.80; P <.0001). The objective response rate with binimetinib was 15%, including 1 complete response, compared with 7% for dacarbazine.”

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Binimetinib Improves PFS in NRAS-Mutated Metastatic Melanoma

Excerpt:

“The novel MEK inhibitor binimetinib resulted in improved progression-free survival (PFS) and response rates vs dacarbazine in patients with NRAS-mutated advanced unresectable/metastatic melanoma, according to results of an open-label phase III trial.

“ ‘NRAS mutations are present in approximately 20% of all patients with metastatic melanoma,’ said Reinhard Dummer, MD, of the University Hospital Zurich in Switzerland. ‘It activates the MAPK pathway and by this drives cell proliferation and anti-apoptotic mechanisms.’ Preclinical studies have shown that NRAS-mutant melanoma is sensitive to MEK inhibition, and binimetinib inhibits both MEK1 and MEK2. A phase II study showed clinical activity in NRAS-mutant metastatic melanoma.

“The NEMO trial included 402 patients randomized 2:1 to receive either binimetinib (269 patients) or dacarbazine (133 patients; 19 were not treated and were not evaluated for safety). Patients were either treatment-naive or had progressed on or after immunotherapy. The primary endpoint of the study was PFS. The results were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting held earlier this month in Chicago (abstract 9500).”

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FDA Approves Frontline Opdivo for Advanced Melanoma

“The approval was based on a substantial improvement in overall survival (OS) in a phase 3 study.

“The FDA has expanded the approval for single-agent Opdivo (nivolumab) to include the frontline treatment of patients with BRAF wild-type advanced melanoma, based on a substantial improvement in overall survival (OS) compared with the chemotherapy dacarbazine in a phase 3 study.

“In the data assessed by the FDA from the CheckMate-066 trial, the median OS with Opdivo was not reached versus 10.8 months for dacarbazine, representing a 58 percent reduction in the risk of death. Median progression-free survival (PFS) with Opdivo was 5.1 versus 2.2 months for dacarbazine.”


New Long-Term Data on Opdivo and the Opdivo + Yervoy Regimen Shows Survival Benefit Across Lines of Therapy in Advanced Melanoma

“Bristol-Myers Squibb Company (NYSE:BMY) today announced new long-term data of Opdivo in treatment-naïve BRAF wild-type advanced melanoma from CheckMate -066. In the trial, Opdivo continued to demonstrate superior overall survival versus dacarbazine with 57.7% of patients alive at two years compared to 26.7% of patients treated with dacarbazine. The safety profile of Opdivo was consistent with prior studies. The two-year survival and safety data from CheckMate -066 represent the longest follow-up from a randomized study of any PD-1 immune checkpoint inhibitor in the first-line setting of advanced melanoma. These data will be presented as a late-breaking presentation at the Society for Melanoma Research (SMR) 2015 International Congress in San Francisco, CA from November 18 to 21.”


Briefer Biochemotherapy Yields Better Relapse-Free Survival but Greater Toxicity vs 1-Year High-Dose Interferon in High-Risk Melanoma

The gist: Compared to a standard treatment, an alternative, shorter treatment for stage III melanoma may lengthen the amount of time patients go without their cancer returning. However, it has more toxic side effects. And compared to the standard, it doesn’t lengthen life. The alternative treatment uses the drugs cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b. In a clinical trial with volunteer patients, it was compared to longer (1-year), high-dose treatment with the drug interferon alfa-2b. The trial involved people aged 10 years and older with stage IIIA-N2a through IIIC-N3 melanoma.

“In a phase III trial (Southwest Oncology Group Intergroup S0008) reported in the Journal of Clinical Oncology, Flaherty et al found that a shorter course of biochemotherapy consisting of cisplatin, vinblastine, dacarbazine, interleukin-2, and interferon alfa-2b produced better relapse-free survival, but not overall survival, and was associated with greater toxicity compared with a 1-year high-dose interferon alfa-2b regimen in patients with high-risk melanoma. The trial is a Cancer and Leukemia Group B, Children’s Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group Intergroup study…

“In the trial, 402 patients aged ≥ 10 years with stage IIIA-N2a through IIIC-N3 melanoma were randomly assigned between September 2000 and November 2007 to receive biochemotherapy plus granulocyte colony-stimulating factor given every 21 days for three cycles (n = 199) or high-dose interferon alfa-2b intravenously 5 days per week for 4 weeks and subcutaneously three times per week for 48 weeks (n = 203). The coprimary endpoints were relapse-free survival and overall survival.

“The high-dose interferon and biochemotherapy groups were generally balanced for age (median, 48 and 46 years), sex (69% and 71% male), race/ethnicity (96% and 95% white), number of involved nodes (1–3 or satellite/in-transit only in 76% in both), nodal involvement (micrometasteses only in 43% and 44%), and ulceration (41% in both)…

“The investigators concluded: ‘Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in [relapse-free survival] but no difference in [overall survival] and more toxicity compared with [high-dose interferon].’ ”


Nivolumab Superior to Dacarbazine for Untreated Metastatic Melanoma

The gist: A recent clinical trial with volunteer patients compared two treatments for metastatic melanoma. It showed that one of the treatments might give longer survival times for people whose tumors do not have mutations in the BRAF gene. This treatment is a drug called nivolumab. It is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. In the trial, some patients took nivolumab and some took the chemotherapy drug dacarbazine. People who took nivolumab lived a few months longer than people who took dacarbazine. None of the patients had taken any previous treatments for their melanoma.

“Patients with treatment-naive, BRAF wild-type metastatic melanoma treated with nivolumab demonstrated longer OS and PFS than those treated with dacarbazine, according to phase 3 study results presented at the Society for Melanoma Research International Congress.

“Prior research showed nivolumab (Opdivo, Bristol-Myers Squibb) — a PD-1 immune checkpoint inhibitor — was associated with higher rates of objective response compared with chemotherapy in patients with ipilimumab (Yervoy, Bristol-Myers Squibb)-refractory disease.

“In the current study, Caroline Robert, MD, PhD, head of the Dermatology Unit at the Institut Gustave-Roussy in Paris, and colleagues compared the efficacy of nivolumab vs. chemotherapy in 418 previously untreated patients.

“Researchers assigned patients 3 mg/kg nivolumab every 2 weeks plus a dacarbazine-matched placebo, or 1,000 mg/m2dacarbazine every 3 weeks plus a nivolumab-matched placebo.”