Sequencing of surgery, immunotherapy impacts outcomes in melanoma
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The sequence of surgery and immunotherapy affects outcomes for patients with melanoma, according to a speaker at Chemotherapy Foundation Symposium.
“We have recently had data emerge for neoadjuvant and adjuvant immunotherapy approaches in patients with melanoma,” Sapna P. Patel, MD, director of the uveal melanoma program and program director of the melanoma fellowship at The University of Texas MD Anderson Cancer Center, said during a presentation.
Neoadjuvant setting
“The randomized phase 2 SWOG S1801 trial established that neoadjuvant pembrolizumab [Keytruda, Merck] extended event-free survival compared with adjuvant-only administration of the anti-PD-1 therapy among patients with stage IIIB to stage IV cutaneous, acral mucosal resectable melanoma,” Patel said.
As Healio previously reported, researchers randomly assigned patients 1:1 to surgery followed by 18 doses of 200 mg pembrolizumab once every 3 weeks or three doses of neoadjuvant pembrolizumab followed by surgery and 15 doses of pembrolizumab once every 3 weeks.
“Surgery in S1801 was prespecified at the time of randomization and was required to be carried out regardless of response in the neoadjuvant arm,” Patel said. “S1801 is not a referendum on de-escalation of surgical therapy — it is simply a question of whether we can alter the sequence of standard treatment.”
Results of the trial showed a 72% EFS rate with neoadjuvant therapy compared with a 49% with adjuvant therapy.
“The benefit favoring neoadjuvant therapy was observed across all subgroups, including age, gender, performance status, stage of melanoma and BRAF mutation status,” Patel said. “By simply resequencing treatment, we were also able to avoid all of the adverse events that normally occur during the adjuvant period. When we swing the same treatment given in the adjuvant setting to the neoadjuvant setting, we see improvements.”
Adjuvant setting
Key results have also been reported in the adjuvant setting, Patel said.
For example, the phase 3 KEYNOTE-716 study showed pembrolizumab significantly improved distant metastasis-free survival among patients with resected stage IIB or stage IIC melanoma.
The KEYNOTE-054 and S1404 trials, which also assessed adjuvant pembrolizumab, included patients with stage IIIA disease who are typically at low risk for recurrence, according to Patel.
“KEYNOTE-054 and S1404 were small, but in S1404, we saw no real difference or trend in benefit with adjuvant pembrolizumab,” Patel said. “For stage IIIB and IIIC disease, the definitive studies — Checkmate 238, S1404 and KEYNOTE-054 — showed the difference in RFS is driven by patients with stage IIIB and stage IIIC disease for all three studies.”
In the IMMUNED study, presented at ESMO this year, researchers randomly assigned patients to nivolumab (Opdivo, Bristol Myers Squibb) plus ipilimumab (Yervoy, Bristol Myers Squibb), nivolumab alone or placebo, Patel said.
“What we saw in terms of recurrence free survival is the initiation of nivolumab plus ipilimumab within 8 weeks of rendering of the patient [as having no evidence of disease] demonstrated an improvement vs. placebo and a strong improvement vs. nivolumab monotherapy,” she said.
Of note, patients with BRAF mutations derived the most benefit with adjuvant therapy.
“Interestingly, the BRAF-mutated subset experienced a strong benefit in both nivolumab groups and significantly with the nivolumab and ipilimumab combination,” Patel said. “This is a theme that we often see across immunotherapy trials — the presence of a BRAF mutation derives a strong benefit from the use of adjuvant therapy.”
Patel said it is also important to note that there is no role for the use of adjuvant nivolumab plus ipilimumab in resected stage IIIB to stage IIID melanoma.
“This role has not been established and essentially was deemed that there was no role for this combination based on the results of the CheckMate 915 study,” she said.
References :
- Ascierto PA, et al. Lancet Oncol. 2020;doi:10.1016/S1470-2045(20)30494-0.
- Eggermont AM, et al. Abstract 9500. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
- Grossmann KF, et al. Abstract 9501. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
- Long GV, et al. Abstract LBA9500. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
- Patel SP, et al. Abstract LBA6. Presented at: European Society for Medical Oncology Congress; Sept. 9-13, 2022; Paris.
- Patel SP, et al. Neoadjuvant and adjuvant therapeutic approaches for melanoma. Presented at: 40th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 9-11, 2022.
- Weber JS, et al. J Clin Oncol. 2022;doi:10.1200/JCO.22.00533.
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Patel SP, et al. Neoadjuvant and adjuvant therapeutic approaches for melanoma. Presented at: 40th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 9-11, 2022.
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