Geoffrey T. Gibney, MD, co-leader of the Melanoma Disease Group, and a member of the Developmental Therapeutics (Phase I) program at the Lombardi Comprehensive Cancer Center and MedStar Cancer Network, MedStar Georgetown University Hospital, discusses the potential utility of fixed-duration immunotherapy in melanoma.

Historically, the pivotal trials for PD-1/PD-L1 inhibitors, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), in melanoma did not evaluate the agents as a time-limited treatment, says Gibney. Instead, the studies indicated that treatment could be continuous, even in patients who were tolerating and responding to the therapy, Gibney explains.

As such, the debate as to whether patients responding to immunotherapy can stop therapy at a prespecified timepoint remains open, Gibney says. However, efforts are ongoing to answer this question. For example, the phase 3 KEYNOTE-006 study evaluated 2 years of pembrolizumab in patients with advanced melanoma. 

It is likely that patients can stop immunotherapy after 2 years; however, since the optimal duration of immunotherapy is still not well defined, many patients receive a longer course of therapy, Gibney says. Additionally, many patients may be able to stop therapy after 1 year, Gibney adds. Time-limited therapy can lower the financial burden of therapy, minimize late-onset toxicities, and eliminate unnecessary visits to the clinic that can put strain on the health care system overall, concludes Gibney.

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Geoffrey T. Gibney, MD, discusses the potential utility of fixed-duration immunotherapy in melanoma.  



Dr. Gibney on the Potential for Fixed-Duration Immunotherapy in Melanoma

Geoffrey T. Gibney, MD, co-leader of the Melanoma Disease Group, and a member of the Developmental Therapeutics (Phase I) program at the Lombardi Comprehensive Cancer Center and MedStar Cancer Network, MedStar Georgetown University Hospital, discusses efforts made to determine the optimal duration of treatment with anti–PD-1 agents in patients with melanoma.

When examining anti–PD-1 therapy in patients with melanoma it is not only important to establish the efficacy of agent, but also to determine how to safely administer it, Gibney says. The optimal duration of therapy has never been well defined, adds Gibney. Many studies that have led to the FDA approvals of agents such as 

 did not have a definitive time established to discontinue treatment in patients who were tolerating the agent well and responding, Gibney explains. Due to this, treatment duration has been a topic of discussion in the community.

In the phase 3 KEYNOTE-006 and phase 1 KEYNOTE-001 trials, treatment with pembrolizumab was discontinued after 2 years of treatment and after 2 subsequent scans showing a complete response, respectively, Gibney notes. However, these studies did not conclusively determine the optimal duration of treatment.

Currently, it is thought that 2 years may be the appropriate treatment duration for anti–PD-1 agents; however, some might consider continuing treatment further, Gibney concludes.

Geoffrey T. Gibney, MD, discusses efforts made to determine the optimal duration of treatment with anti–PD-1 agents in patients with melanoma.

Dr. Gibney on Determining Optimal Treatment Duration With Anti–PD-1 Agents in Melanoma

Geoffrey T. Gibney, MD, co-leader, Melanoma Disease Group and a member of the Developmental Therapeutics (Phase I) program at the Lombardi Comprehensive Cancer Center and MedStar Cancer Network, MedStar Georgetown University Hospital, discusses selecting between BRAF inhibitor regimens in melanoma. 

-mutant unresectable stage III or active stage IV melanoma can receive BRAF-targeted therapy or immunotherapy with anti–PD-L1 agents, Gibney explains.

If targeted therapy is selected, choosing between available BRAF inhibitor combinations can be challenging, says Gibney. 

Currently, 3 doublets are approved by the FDA for this indication: dabrafenib (Tafinlar)/trametinib (Mekinist), encorafenib (Braftovi)/binimetinib (Mektovi), and vemurafenib (Zelboraf)/cobimetinib (Cotellic).

Data show similar rates of efficacy with these regimens, Gibney says. Although slight differences in toxicities have been observed, the rates of serious grade 3 or 4 toxicities are comparable. Moreover, around 15% of patients permanently discontinue treatment irrespective of which regimen is used. 

As such, dosing schedules, individual toxicities, and patient preference play significant roles in informing the optimal regimen, concludes Gibney.

Geoffrey T. Gibney, MD, discusses selecting between BRAF inhibitor regimens in melanoma.  



Geoffrey Thomas Gibney, MD, MedStar Georgetown University Hospital

Articles

Dr. Gibney on the Potential for Fixed-Duration Immunotherapy in Melanoma

Dr. Gibney on Determining Optimal Treatment Duration With Anti–PD-1 Agents in Melanoma

Dr. Gibney on Selecting Between BRAF Inhibitor Regimens in Melanoma