Melanoma

In an interview with Targeted Oncology, Pier Francesco Ferrucci, MD, discussed the findings from the updated analysis, which he shared in a presentation at the 16th International Congress of the Society for Melanoma Research, highlightening the important takeaways from this follow-up analysis.

Georgina V. Long, BSc, PhD, MBBS, FRACP, discusses the current treatment options that are approved around the world for patients with advanced melanoma. These treatments include both immunotherapies, such as immune checkpoint inhibitors, and targeted therapies.

The combination of atezolizumab, cobimetinib, and vemurafenib reduced the risk of disease progression or death compared with placebo in patients with BRAF V600 mutation-positive advanced melanoma, meeting the primary endpoint of progression-free survival in the phase III IMspire150 study, according to a press release from Roche.

Treatment with immunotherapy has become ingrained in the standard of care for treating patients with melanoma, but investigators continue to research new combinations and treatment strategies that can improve patients outcomes. One approach that has generated a great deal of interest and is a significant focus of ongoing trials involves adjuvant and neoadjuvant therapy, according to Jeffrey S. Weber, MD, PhD.

Adil Daud, MD, compares the roles of immunotherapy versus dabrafenib plus trametinib targeted therapy combinations in patients with advanced melanoma. The latter combination is appropriate and even preventative in select patients, but the decision between checkpoint immune therapy and immunotherapy comes down to what is best for each patient.

The combination of nivolumab with ipilimumab showed no statistically significant benefit in patients with stage IIIB/C/D or stage IV melanoma compared with nivolumab alone in the phase III CheckMate 915 study, missing the co-primary endpoint of recurrence-free survival  in patients with <1% PD-L1 expression in their tumor cells, according to a press release from Bristol-Myers Squibb.

Thomas Marron, MD, discusses the rationale for investigating immunotherapy discontinuation in patients with melanoma.

In an interview with Targeted Oncology, Jeffrey S.Weber, MD, PhD, discussed the 3-year efficacy and biomarker results from the phase III CheckMate 238 trial, which he presented at the 2019 European Society of Medical Oncology Congress.

The use of CMP-001, an intratumoral toll-like receptor 9 agonist, is capable of triggering durable responses when used in combination with pembrolizumab for patients with PD-1 resistant metastatic melanoma according to results from a phase Ib study presented at the Society for Immunotherapy of Cancer’s 34th Annual Meeting.

Immunotherapies and targeted therapies have greatly impacted the treatment of advanced melanoma and are beginning to make their way into earlier settings, with FDA approvals for adjuvant therapies and studies ongoing in the neoadjuvant space, according to a presentation by Jeffrey S. Weber, MD, PhD, at the <em>37th Annual</em> CFS.

During a <em>Targeted Oncology </em>live case-based peer perspectives live discussion, Anna C. Pavlick, DO, MS, explained to a group of physicians best practices for the diagnosis and management of patients with metastatic melanoma. Pavlick, discussed treatment options between immunotherapy and targeted therapy based on the case scenario of a patient with <em>BRAF </em>wild-type metastatic melanoma.

Ryan Sullivan, MD, discusses the 5-year data pooled from the phase III COMBI-d and COMBI-v trials, which each studied dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with&nbsp;<em>BRAF V600</em>&ndash;mutant unresectable or metastatic melanoma.

&ldquo;New therapies have increased the median survival for advanced-stage melanoma from approximately 9 months before 2011 to at least 2 years, based on [data from] clinical trials,&rdquo; Elizabeth Ward, PhD, and colleagues wrote about their report on cancer burden in younger patients.

In a recent review of the 5-year outcomes from the COMBI-d and COMBI-v trials published in the&nbsp;New England Journal of Medicine, investigators saw long-term benefit with the use of dabrafenib plus trametinib as first-line treatment in about one-third of patients with unresectable or metastatic melanoma and&nbsp;BRAF V600E or V600K mutations.

Keith T. Flaherty, MD, discusses the combination regimens and the potential role for a 3-drug regimen as treatment for patients with melanoma. He says investigators have been searching for new combination strategies beyond the combination of BRAF and MEK inhibitors.

In an interview with&nbsp;Targeted Oncology, Shailender Bhatia, MD, highlighted the key takeaways from the 5 abstracts he found most significant at the 2019 ASCO meeting for the treatment of patients with melanoma.

In an interview with <em>Targeted Oncology</em>, Michael Atkins, MD, discussed the latest follow-up data from the combination of nivolumab and ipilimumab across 2 trials and next steps in the research with this combination for patients with advanced melanoma.

The combination of bempegaldesleukin and nivolumab was granted a breakthrough therapy designation by the FDA&nbsp;for the treatment of patients with previously untreated unresectable or metastatic melanoma.

David Polsky, MD, PhD, discusses the findings from a liquid biopsy analysis of the COMBI-d trial, which is a phase III trial investigating the combination of dabrafenib and trametinib or dabrafenib alone in patients with BRAF V600E/K&ndash;mutant melanoma. Investigators found an association between the presence of baseline circulating tumor DNA (ctDNA) and a poor prognosis with the treatment of BRAF inhibitors.

In an interview with&nbsp;Targeted Oncology, Rodabe N. Amaria, MD, discussed the guidelines and recommendations outlined by the INMC. She also highlighted the importance of genomic testing in the neoadjuvant setting of melanoma.&nbsp;

In an interview with&nbsp;<em>Targeted Oncology</em>, David Polsky, MD, PhD, discussed the findings from this analysis in patients with&nbsp;<em>BRAF</em>-mutant, unresectable, metastatic melanoma. He highlighted the next steps necessary for validating these findings and potentially using ctDNA to help inform treatment decisions for patients with metastatic melanoma.

The FDA has accepted 6 supplemental Biologics License Applications (sBLAs) for review for a potential update to the dosing schedule for pembrolizumab across several indications.

The ability to activate pattern recognition receptors, carry other genetic &ldquo;cargo&rdquo; to modify immunity, and induce lymphocyte infiltration into cancer is an appealing strategy accomplished by intralesional oncolytic viruses. Thus, the concept of combining these novel therapeutics in the preoperative setting to enhance in situ immunization and antitumor activity systemically, as well as to increase R0 complete resection, may be a useful approach to lead to cure, according to Robert L. Ferris, MD, PhD.

Nikhil I. Khushalani, MD, discusses the rationale for combining nivolumab with bempegaldesleukin for the treatment of patients with newly diagnosed, unresectable or metastatic melanoma in a randomized, open-label phase III trial.

Biomarker expansion has enjoyed a boom since 2006, with patient incidence of positive biomarkers reaching up to 50% in non&ndash;small cell lung cancer and melanoma and 25% in acute myeloid leukemia and myelodysplastic syndromes, according&nbsp; to the <em>Global Oncology Trends 2018</em> report.

The phase III IMspire170 trial failed to meet its primary endpoint according to topline results from the study. The combination of atezolizumab and cobimetinib did not improve progression-free survival compared with pembrolizumab in patients with previously untreated<em> BRAF&nbsp;</em>V600 wild-type melanoma.

<em>Targeted Oncology</em>&nbsp;spoke with experts in attendance at the 2019 ASCO Annual Meeting to review what they believed were some of the biggest takeaways from this year&#39;s presentation across the fields of lung cancer, breast cancer, GI cancers, genitourinary cancers, melanoma, and multiple myeloma.

Neoadjuvant&nbsp;talimogene laherparepvec (T-VEC) led to a significant improvement in the 1-year recurrence-free survival rate in patients with resectable advanced melanoma compared with surgery alone, according to a randomized trial presented at the 2019 ASCO Annual Meeting.

The investigational PD-1 inhibitor spartalizumab demonstrated a high rate of complete responses in combination with&nbsp;dabrafenib and trametinib in&nbsp;patients with previously untreated advanced&nbsp;<em>BRAF&nbsp;</em>V600&ndash;mutant melanoma. Patients pooled from 2 parts of the 3-part COMBI-i study demonstrated a CR rate of more than 40%.

Keith T. Flaherty, MD, director, Termeer Center for Targeted Therapy, Massachusetts General Hospital Cancer Center, professor of medicine, Harvard Medical School, shares updated overall survival data from the phase III COLUMBUS trial examining encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma.