Melanoma: New Drugs and New Challenges (Part 1 of 2)


New targeted and immunotherapy drugs have changed the diagnosis of metastatic melanoma from a death sentence into a disease that can potentially be managed and even cured. Nevertheless, these new drugs do not work in all patients, or they may stop working after a transient response. This post (part one of two) will describe ongoing efforts to find drug combinations with higher efficacy than single drugs and decipher the mechanisms underlying drug resistance. Continue reading…


Considerations for Single-Agent Versus Combo Melanoma Immunotherapy

Excerpt:

“The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) continues to show promise, with recent data demonstrating a 26% improvement in overall survival (OS) with the 2 drugs compared with ipilimumab alone for patients with advanced melanoma.

“In a 2-year assessment of the phase II CheckMate-069 trial, which was recently presented at the 2016 AACR Annual Meeting, 142 treatment-naïve patients with unresectable stage III or metastatic stage IV melanoma were randomized to receive either the combination (n = 95) or ipilimumab plus placebo (n = 47) every 3 weeks for 4 doses followed by nivolumab or placebo every 2 weeks until disease progression or unacceptable toxicity.

“In the overall treatment population, the 2-year OS rate was 64% with the combination compared with 54% for ipilimumab alone (HR, 0.74; 95% CI, 0.43-1.26). The median OS at 2 years in patients randomized to either the combination or monotherapy has not been reached.”

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Understanding the Future of Immunotherapy in Melanoma

Excerpt:

“While there have been many recent advances in the field of melanoma regarding immunotherapy, there is much more is to come, says Antoni Ribas, MD, PhD.

“One notable breakthrough, which demonstrates the significant potential of the field, is the phase II CheckMate-069 trial, which examined the combination of ipilimumab (Yervoy) and nivolumab (Opdivo). The combination showed a 42% improvement in overall survival (OS) when compared with ipilimumab as a monotherapy.

“In an interview with Targeted Oncology, Ribas, a professor of Medicine, Surgery, and Molecular and Medical Pharmacology at the University of California, discusses what these data mean and where the field of immunotherapy in melanoma is headed.”

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Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.


Nivolumab/Ipilimumab Combination FDA Approved for BRAF Wild-Type Melanoma

“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.

” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”


Video: Efficacy of PD-1/PD-L1 Inhibitors in Melanoma

“Jason J. Luke, MD, FACP, assistant professor of medicine, The University of Chicago, discusses the efficacy of PD-1/PD-L1 inhibitors in melanoma. The combination of these inhibitors, nivolumab and ipilimumab, was used to treat patients with previously untreated, unresectable or metastatic melanoma, in the Checkmate 069 study.

“Luke says PD-L1 is very complex and difficult when developing immunohistochemical assays. Since several pharmaceutical companies conduct different assays that test various things, a particular patient may be positive in one case, but not in another. For this reason, patients become very confused.

“Luke also mentions that there is no validated method across the board, so it is difficult to determine the next steps going forward.”