Neoadjuvant immunotherapy improves outcomes of patients with high-risk melanoma (Pembrolizumab before and after surgery = 42% lower event rate)

Medical Xpress / University of Texas M. D. Anderson Cancer Center / New England Journal of Medicine ^ | March 1, 2023 | Sapna Patel, M.D. et al

[ConservativeMind]

Patients with high-risk melanoma who received the immunotherapy drug pembrolizumab both before and after surgery to remove cancerous tissue had a significantly lower risk of their cancer recurring than similar patients who received the drug only after surgery.

"It's not just what you give, it's when you give it. The S1801 study demonstrates the same treatment for resectable melanoma given before surgery can generate better outcomes," Patel said. "In this case, we used the immune checkpoint inhibitor pembrolizumab."

The mechanism of action of immune checkpoint inhibitors such as pembrolizumab is often described as "taking the brakes off" the immune system's response to tumor cells.

To test this hypothesis, S1801 investigators enrolled 345 participants with stage IIIB through stage IV melanoma that was deemed operable. Participants ages 18–90 were randomized to receive either upfront surgery followed by 200 mg of pembrolizumab every three weeks (adjuvant-only) for a total of 18 doses, or to 200 mg of pembrolizumab every three weeks for three doses leading up to surgery (neoadjuvant-adjuvant), then an additional 15 doses following surgery.

The primary endpoint measured was the duration of event-free survival.

With a median follow-up of 14.7 months, event-free survival was significantly longer in the neoadjuvant-adjuvant therapy arm, with a hazard ratio of 0.58 when compared to the adjuvant therapy arm, which corresponds to a 42% lower event rate in the patients receiving the neoadjuvant regimen.

"Our study noted a significant improvement in event-free survival in the neoadjuvant regimen compared to the adjuvant regimen," Patel said.

"Based on the findings from S1801, patients with high-risk melanoma should start immunotherapy prior to surgery to generate an immune response while the bulk of the melanoma and the anti-tumor T cells are intact," Patel said.

[ConservativeMind]

A lot fewer events happened with pembrolizumab before, and after, surgery.

[ConservativeMind]

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[BBB333]

Mrs. BBB333 was asked to take part in this study in 2020 (her 2015 stage 2B melanoma had metastasized into stage 3C in late 2020).

For several reasons she declined the invitation — the biggest was her immense fear of needles. She chose to take pembrolizumab every six weeks @ 400 mg per dose thus reducing the number of infusions by 9.

Mrs. BBB333 had her two egg sized tumors removed from the outside and inside of her left pelvis along with 17 lymph-nodes, five of which were positive for a strain of Non-Hodgkins Lymphoma (microscopic). This discovery would have forced her removal from the study.

She is doing well two years after the surgery and her Lymphoma is still microscopic and is contained to her GI tract according to her last several PET scans.

We are enjoying our time together and have several trips planned this summer.

Thanks for posting this article.