March 2023

ONCOLOGY

PRE-SURGERY IMMUNOTHERAPY MAY INCREASE SURVIVAL IN ADVANCED MELANOMA

Featuring: ​Sunandana Chandra, MD, MS

Patients with high-risk, advanced-stage melanoma who received the immunotherapy drug pembrolizumab both before surgery (neoadjuvant) and after surgery (adjuvant) had longer event-free survival than patients who received immunotherapy only after surgery according to a recent clinical trial published in the New England Journal of Medicine.

“This showed us for the first time in a randomized trial design that timing of surgery really does matter,” said Sunandana Chandra, MD, MS, associate professor of Medicine in the Division of Hematology and Oncology and a co-author of the study.

In the current phase two clinical trial, patients with high-risk stage III or stage IV melanoma were randomly assigned to either receive neoadjuvant pembrolizumab for nine weeks, followed by surgery, and then followed by adjuvant pembrolizumab for a total of one year; or to undergo surgery followed by adjuvant pembrolizumab only for one year or until their disease recurred or they experienced adverse events.

The primary endpoint was event-free survival and adverse events included disease progression, toxic effects that prevented surgical resection or prevented the initiation of adjuvant therapy, surgical complications, melanoma recurrence after surgery and death from any cause.

After a 15-month follow-up, the combined neoadjuvant–adjuvant group demonstrated significantly longer event-free survival than the adjuvant-only group. Notably, event-free survival at two years was 72 percent in the neoadjuvant–adjuvant group compared to just 49 percent in the adjuvant-only group.  

Overall, the findings suggest that neoadjuvant-adjuvant pembrolizumab can significantly improve event-free survival for patients with advanced melanoma without added toxic effects.  

Chandra added that the findings can help change the way clinicians think about sequencing therapy and surgery, but additional questions remain and warrant further investigation.

“Now that we have this intriguing data showing that the sequencing of immunotherapy and surgery does matter, some questions we have are: do we even need the post-surgery adjuvant therapy, and for how long? Would we potentially in the future be able to deescalate surgery to minimize surgical morbidity? Will this approach lead to an overall survival benefit?” Chandra said.

“Most importantly, I would like to thank our patients and their family members for their trust in us and their participation in the trial. Our patients’ participation and engagement in these kinds of trials is the only way that the field of melanoma is going be able to move forward,” Chandra said.

Jeffrey Sosman, MD, professor of Medicine in the Division of Hematology and Oncology, was also a co-author of the study. 

Chandra and Sosman are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

This work was supported by grants from the National Cancer Institute of the National Institutes of Health (U10CA180888, U10CA180819, U10CA180820, U10CA180821, U10CA180868, UG1CA233329, UG1CA233328, UG1CA233247, UG1CA233180, UG1CA189860, UG1CA233178, UG1CA233160, UG1CA189821, UG1CA233320, UG1CA233331, UG1CA189850, UG1CA233330, UG1CA233234, UG1CA233193, UG1CA189956, UG1CA239767, UG1CA189869, UG1CA180830, P30CA014089, UG1CA239758, P30CA016042, UG1CA189830, P30CA076292, P30CA033572, R35 CA197633 and P01 CA244118) and in part by Merck Sharp and Dohme, a subsidiary of Merck.
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This article was originally published in the Feinberg School of Medicine News Center on March 23, 2023. ​
Sunandana Chandra, MD, MS, associate professor of Medicine in the Division of Hematology and Oncology, was a co-author of the study published in the New England Journal of Medicine.
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