Melanoma

The FDA approved several indications in the month of June, including venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), the combination of binimetinib (Mektovi) plus encorafenib (Braftovi) in melanoma, and bevacizumab (Avastin) in ovarian cancer. The FDA also accelerated approvals for pembrolizumab (Keytruda) in cervical cancer and in primary mediastinal large B-cell lymphoma, while also granting a priority review to glasdegib for acute myeloid leukemia.

Based on findings from the phase III CheckMate-238 trial, nivolumab (Opdivo) has been recommended for approval by the European Medicines Agency’s Committee for Medicinal Products for Human Use as an adjuvant treatment for adult patients with completely resected melanoma with lymph node involvement or metastatic disease, according to Bristol-Myers Squibb, the developer of the PD-1 inhibitor.

The combination of&nbsp;the BRAF inhibitor encorafenib (Braftovi) and the MEK inhibitor binimetinib (Mektovi) has been approved by the FDA&nbsp;for the treatment of patients with<em>&nbsp;BRAF</em>-mutant unresectable or metastatic melanoma, as detected by an FDA-approved test.&nbsp;The approval is based data from the phase III COLUMBUS trial.

A supplemental&nbsp;biologics license application for the use of pembrolizumab as an adjuvant treatment for patients with resected, high-risk stage III melanoma has been accepted by the FDA,&nbsp;according to Merck, the manufacturer of the PD-1 inhibitor.

Pembrolizumab (Keytruda) induced a median overall survival (OS) of 32.7 months versus 15.9 months for ipilimumab (Yervoy) in patients with unresectable stage III-IV melanoma, according to 4-year survival results from the KEYNOTE-006 trial presented at the 2018 ASCO Annual Meeting.

Alexander M. Eggermont, MD, PhD, director general of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the history of immune checkpoint inhibitors in the treatment landscape of melanoma.

Researchers&rsquo; understanding of why patients with cancer do or do not respond to treatment with immune checkpoint inhibition is constantly evolving, with new developments in innate and adaptive immunity, the tumor microenvironment, and more changing the way that immunotherapy is viewed and used. Many researchers are now pointing to the effect that gut microbiota have on patients&rsquo;&nbsp;response to checkpoint inhibitors and its implications for the treatment of patients receiving immunotherapy.

According to updated data from the phase I/II PIVOT-02 trial presented at the 2018 ASCO Annual Meeting, the combination of NKTR-214 plus the PD-1 inhibitor nivolumab demonstrated promising antitumor activity in patients with advanced solid tumors, particularly in PD-L1&ndash;negative patients.

Keith T. Flaherty, MD, professor of Medicine, Harvard Medical School, director of Clinical Research, Massachusetts General Hospital, discusses overall survival results from the phase III COLUMBUS trial investigating encorafenib plus binimetinib versus vemurafenib (Zelboraf) or encorafenib in BRAF-mutant melanoma during the 2018 ASCO Annual Meeting.

According to findings of the IMPACT study discussed at the 2018 ASCO Annual Meeting, overall survival was improved with personalized therapy based on tumor molecular profiling in patients with advanced, hard-to-treat cancers.

Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center at NYU Langone Medical Center, discusses the adverse events commonly associated with the combination of dabrafenib and trametinib in the adjuvant setting for patients with BRAF V600E&ndash; or V600K&ndash;positive stage III melanoma.

Adjuvant therapy for melanoma to lower the risk of disease recurrence and death in patients with high-risk disease who have undergone definitive surgical treatment has previously been administered primarily to patients with stage III disease, as well as a small group of patients with stage IV disease who could be rendered disease free surgically, according to Ahmad A. Tarhini, MD, PhD.

Ahmad Tarhini, MD, PhD, director of the Melanoma and Skin Cancer Program and Immune-Oncology Research at the Cleveland Clinic Taussig Cancer Institute, discusses 3 recent trials that are changing the adjuvant treatment landscape of melanoma. The treatments presented in these trials have less toxicities overall and less impact on the quality of life, according to Tarhini.

The FDA approved several indications throughout the month of April 2018.&nbsp;A number of drugs were granted priority review and Fast Track designation. The FDA also halted all clinical trials using&nbsp;tazemetostat as treatment, and new initiatives were introduced&nbsp;to help ease the development of genetic and genomic-based tests.&nbsp;Check out our list of all FDA happenings from April 2018.

A new set of National Comprehensive Cancer Network guidelines have been created for the diagnosis and management of uveal melanoma. During the 2018 NCCN Annual Conference, a member of the NCCN Melanoma Subcommittee, Christopher A. Barker, MD, presented the inaugural guidelines as &ldquo;the first pathway-based guidelines&rdquo; to be developed for the disease.

Based on data from the phase III COMBI-AD study, the combination of&nbsp;dabrafenib and trametinib has been granted FDA approval for&nbsp;the adjuvant treatment of patients with BRAF V600E&ndash; or V600K&ndash;positive stage III melanoma following complete resection.

A 4-week dosing schedule for&nbsp;nivolumab has been approved by the European&nbsp;Commission&nbsp;for the treatment of patients with advanced melanoma and previously treated renal cell carcinoma, Bristol-Myers Squibb (BMS), the manufacturer of the PD-1 inhibitor, has announced.

According to phase Ib study findings presented at the 2018 AACR Annual Meeting, combining the&nbsp;intratumoral toll-like receptor 9 (TLR9) agonist&nbsp;CMP-001 and pembrolizumab showed clinical activity in reversing&nbsp;PD-1 checkpoint inhibition resistance in patients with metastatic melanoma.

Alexander M. M. Eggermont, MD, PhD, director general&nbsp;of Gustave Roussy Cancer Campus Grand Paris in Villejuif, France, discusses the phase III results from the EORTC 1325-MG/KEYNOTE-054 trial presented at the 2018 AACR Annual Meeting.

According to the results from a phase I study, BLU-667, a next-generation tyrosine kinase inhibitor, was well-tolerated and demonstrated clinical benefit in patients with advanced,&nbsp;<em>RET</em>-altered solid tumors who had progressed on previous therapies. These findings were presented April 14 to 18 at the ASCR Annual Meeting 2018 in Chicago, Illinois.

According to phase III results from the EORTC 1325-MG/KEYNOTE-054 trial presented at the 2018 AACR Annual Meeting and published in the <em>New England Journal of Medicine, </em>adjuvant pembrolizumab (Keytruda) reduced the risk of recurrence or death by 43% in&nbsp;patients with resected, high-risk stage III melanoma.

According to findings from the phase III ECHO-301/KEYNOTE-252 trial, progression-free survival was not improved with the combination of&nbsp;the PD-1 inhibitor pembrolizumab (Keytruda) and the IDO1 inhibitor epacadostat versus single-agent&nbsp;pembrolizumab in patients with unresectable or metastatic melanoma.

Jason J. Luke, MD, assistant professor of medicine at the The University of Chicago Medicine, discusses the importance of conducting research into less common subsets of melanoma. After giving a talk on non-cutaneous melanoma, a rare subtype, Luke explained that not all cases of melanoma arise on the skin and shared why more research is necessary in the field.

The new drug application for larotrectinib (LOXO-101) for treatment of patients with locally advanced or metastatic solid tumors that harbor an NTRK gene fusion&nbsp;has been completed.&nbsp;

The FDA has approved a 4-week dosing schedule for the PD-1 inhibitor nivolumab (Opdivo) across several indications.