Standardization Arrives for Neoadjuvant Trials in Melanoma

August 6, 2019

The new recommendations will help standardize neoadjuvant clinical trial methodology and develop a path for regulatory review and approval of neoadjuvant therapies in melanoma.

The International Neoadjuvant Melanoma Consortium (INMC) recently published a comprehensive set of recommendations for the design and implementation of clinical trials that aim to assess neoadjuvant therapy in high-risk resectable melanoma patients in Lancet Oncology.

Although neoadjuvant therapy is the standard of care for several cancer types, it is only emerging as a potential approach for high-risk resectable melanoma patients. This set of recommendations could help standardize neoadjuvant clinical trial methodology and develop a path for regulatory review and approval of neoadjuvant therapies in melanoma. The INMC detailed a slew of recommendations for a variety of areas, including patient selection, duration of neoadjuvant and adjuvant treatment, trial endpoints, and biospecimen collection.

In terms of patient selection, the INMC “generally” recommended the inclusion of only patients with clinically measurable and surgically resectable stage III disease. Patients with resectable in-transit metastases or oligometastatic stage IV melanoma and borderline-resectable disease may be included in a trial, but only as a separate cohort. The INMC also recommended the duration of neoadjuvant therapy to last between 6 and 8 weeks and adjuvant therapy to last 1 year. 

In addition, although surgical resection is the standard of care for stage III disease, the INMC recommended to “strongly consider” enrolling these patients in a clinical trial to receive neoadjuvant therapy.

“To have a more standard approach with similar endpoints and similar patient criteria will make it easier both for the regulatory groups to compare the results of a trial and for the community clinician to also translate this into their own clinic for practice,” Daniel Wang, MD, medical oncology and a member of the Dan L Duncan Comprehensive Cancer Center at Baylor, told Cancer Network. Wang was not involved in developing the INMC recommendations.

Wang said that the recommendations highlight what the field feels is important concerning both the use of neoadjuvant therapy in melanoma and the standardization of clinical trials so that the field can move forward with newer treatments.

“It will be extremely helpful for future clinical trials to follow this model and sufficiently tackle all the different criteria that they mentioned,” Wang said.

Wang also said he agrees with the recommendation to consider allowing stage III patients into a clinical trial, describing it as a “reasonable approach.”  However, he stressed it’s important to select the right patients and make sure the patient doesn’t miss the window for surgery.

The INMC highlighted the importance of thoroughly assessing pathological response because “pathological responses have been shown to be a robust and crucial predictor of outcomes of neoadjuvant systemic therapy in other cancer types.” The INMC also recommended collecting both tumor and blood samples as various time points as well as collecting gut microbiome samples because, according to previous studies, the gut microbiome may contribute to therapeutic response in melanoma patients.

“I think having some of these prospective specimens and studies done in this setting is going to be really valuable later on as we try to figure out why patients are responding [and] why these drugs are working,” said Wang.