Omid Hamid, MD
Treatment options are expanding in the setting of metastatic melanoma. In January, the National Comprehensive Cancer Network (NCCN) revised its melanoma treatment guidelines to include pembrolizumab and nivolumab, along with ipilimumab, among the preferred systemic options for patients with advanced or metastatic disease.1
These immunotherapy advances are among the emerging treatment approaches that make it an exciting time for patients with melanoma and their physicians, according to experts who participated in a recent OncLive
Peer Exchange program.
Led by moderator Omid Hamid, MD
, the panel of clinical and research experts discussed the evolving treatment of metastatic melanoma during a Peer Exchange session entitled “Updates on the Treatment of Malignant Melanoma.”
An increased understanding of tumor pathology and immunology has led to seven new melanoma drug approvals since 2011, including the recent approvals of the PD-1 inhibitors nivolumab and pembrolizumab. In addition, several completed and ongoing trials show promise that these immunotherapies will improve survival for patients with melanoma. The integration of immunotherapy is still evolving, and the panel discussed several key issues related to its current and future use.Who Will Respond?
Although much progress has been made with immunotherapy, there are still no definite predictors for response to agents that inhibit PD-1 or its ligand PD-L1. Richard W. Joseph, MD
, described a retrospective study of patients on pembrolizumab.2
The researchers “quantified to baseline tumor size in every patient and found out that that was the number one independent prognostic factor, both for survival as well as for response.”
Richard W. Joseph, MD
Questions remain whether PD-1 or PD-L1 expression should be used as a predictive marker for nivolumab and pembrolizumab. Howard L. Kaufman, MD, FACS
, explained that even though “there are increasing data coming out to suggest that PD-L1 expression is associated with the higher response rate...the corollary is that even though the response may be lower in the PD-L1-negative [tumors], there are still some patients who will respond.”3
Assessing Response and Progression
Howard L. Kaufman, MD, FACS
With several immunotherapies available for the treatment of malignant melanoma, oncologists are challenged with assessing treatment response. Anna C. Pavlick, DO,
explained that there can be a “lot of angst when you have to decide, is someone having true progression or is someone having what we know as pseudo-progression, which is essentially an inflammatory response, an immunologic response to the therapy around the tumors where things look worse but the patient is actually responding.” It is not uncommon for patients to have new lesions develop and other lesions get larger before responding to therapy, Robert H.I. Andtbacka, MD, CM,
explained. For instance, in the phase III OPTiM study4
looking at talimogene laherparepvec (TVEC), an intralesionally administered oncolytic vaccine, almost half of patients who ultimately achieved a durable response had growth of their initial melanoma beforehand, said Andtbacka, who helped lead the study.
Other situations that challenge response assessment with immunotherapy include late responders and responders who have persistent lesions. With persistent lesions, a PET scan can verify the patient’s response and isolated persistent lesions can even be treated with surgery or radiotherapy.
Pavlick explained that when assessing how a particular patient is faring on therapy, the patient’s condition is the most important factor, with imaging results and laboratory values being secondary. For example, she said that if a patient appears to be stable or improving but the scan looks worse, she typically tracks the patient for another 6 to 8 weeks to assess disease progression. Joseph added that if the patient was taking a PD-1 inhibitor, he would repeat the scan in 12 weeks, unless there is clinical deterioration.