Pre-Surgical Immunotherapy Identifies Potential Benefit, Risk of Recurrence in Melanoma

For patients with melanoma, administration of a PD-1 checkpoint blockade therapy in the neoadjuvant setting — meaning it was given before the main treatment – could result in improved outcomes, according to study results presented at the 2018 American Association for Cancer Research (AACR) Annual Meeting.

In addition, the researchers, from the University of Pennsylvania in Philadelphia, found that in giving patients Keytruda (pembrolizumab) before surgery, it also provided information about which patients will benefit and which may be facing an increased recurrence risk.

“Our data suggest that giving patients this therapy before surgery may give us a sense of whether or not therapy will be effective against surgery,” Alexander C. Huang, M.D., instructor of Hematology-Oncology in the University of Pennsylvania’s Perelman School of Medicine, said in a press release.

In previous research, Huang and colleagues found that the effect of anti-PD-1 therapy can be seen in patients’ blood as early as three weeks after treatment. Therefore, they investigated whether neoadjuvant administration of anti-PD1 therapy followed by complete resection at three weeks and adjuvant therapy would be a safe and clinically effective approach for patients with high risk resectable melanoma.

Giving immunotherapy upfront is different than current standard of care for resectable melanoma, which includes surgery first, followed by a year of drug treatment in select high risk patients, which can include immunotherapy.

The trial included 27 patients with stage 3 or 4 resectable melanoma who were all given a single 200 mg dose of Keytruda before surgery, followed by curative intent resection three weeks after. After assessment, patients continued to receive one year of adjuvant Keytruda.

Eight patients (30 percent) had a complete or near-complete response after the single dose that was detected at the time of surgery. Of note, the patients who experienced an early response still recurrence-free.

“We were reassured to see that patients who have an early response appear to remain disease-free,” Tara C. Mitchell, M.D., assistant professor of Hematology Oncology at Penn’s Abramson Center and the study’s lead author said in an interview with CURE.

However, not everyone responded as well. For those who did not respond to the drug, more than half of them faced disease recurrences after a year.

In addition, patients with a high degree of tumor-infiltrating lymphocytes (TILs) tended to have longer recurrence-free survival. A TIL is essentially an immune cell that has entered a patient’s tumor. Previous studies have marked high TIL numbers as a sign that the immune system is, indeed attacking the cancer.

When the researchers compared tumor tissue from pre-treatment biopsies to tissue removed during surgery three weeks later, they found an increase in CD8 T cells (a type of tumor-infiltrating cell) as well as PD-L1 expression. This means that the immune system was already kickstarted to fight the cancer.

“This work allows us to turn our focus to patients who may not be benefitting, to learn more about how to ultimately improve outcomes for all patients,” Mitchell said.

Findings from this study lay the groundwork for future studies examining mechanisms of treatment resistance and patients who did not initially respond to immunotherapy treatment.

“We need to focus on studying the patients who did not have an early response in order to improve outcomes for all patients,” Mitchell said.