PRADO Confirms High Ipilimumab–Nivolumab Response In Stage III Melanoma

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: Results of the PRADO study confirm that patients with stage III melanoma respond well to neoadjuvant treatment with two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg, allowing some to omit therapeutic lymph node dissection (TLND). 

Furthermore, the “major subset” of patients that do not undergo this surgery report significantly better quality of life than those who undergo TLND, Christian Blank, from the Netherlands Cancer Institute in Amsterdam, reported at the virtual 2020 ASCO Annual Meeting. 

He explained that PRADO is an extension cohort of the multicentre phase II OpACIN-neo trial, which previously identified ipilimumab 1 mg/kg plus nivolumab 3 mg/kg every 3 weeks for two cycles as the optimal treatment regimen in patients with stage III melanoma. 

The aims of the current study were to confirm the efficacy and safety of this regimen and also to test response-driven subsequent therapy. 

In all, 99 patients (median age 58 years, 66% male) underwent marker placement in the index LN and were then treated with two cycles of neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg.  

At week 6, the index LN was removed from each patient and analysis showed a pathological response rate of 71%. This included 50% with a pathological complete response (pCR; no viable tumour cells), 11% with a near-pCR (≤10% viable tumour cells) and 10% with a pathological partial response (pPR; >10–≤50% viable tumour cells). 

The resulting major pathological response rate (MPR; pCR plus near-pCR) was 61%, which Christian Blank noted is “more than twice the percentage [of] what we see from anti-PD-1 monotherapy in the neoadjuvant setting.” 

The vast majority (98%) of the patients with an MPR went straight to computed tomography and ultrasound follow-up every 12 weeks. One patient underwent surgery despite achieving a near-pCR because of an unfavourable pathological feature in the index LN. 

Eight of the 10 patients achieving a pPR underwent TLND as per the protocol, the remaining two chose not to have surgery. In addition, all 21 nonresponders underwent TLND, 17 initiated adjuvant nivolumab (n=8) or BRAF-targeted therapy (n=9), and seven received additional radiotherapy. Four nonresponders were not given adjuvant therapy due to toxicity from the neoadjuvant therapy. 

Christian Blank said that “[t]he first event-free survival and relapse-free survival data are planned to be presented at this year's ESMO 2020.” 

He also reported that 22% of patients experienced grade 3 or 4 immune-related adverse events (AEs), which “was similar to what was seen in the OpACIN-neo [trial]”. The most common grade 3 or 4 AEs were raised alanine aminotransferase and aspartate aminotransferase levels (7% and 5%, respectively) followed by diarrhoea (5%) and colitis (4%). 

Just over half (54%) of all patients experienced a surgery-related AE, but subanalysis showed that the rate was 41% among the patients who only underwent the index LN procedure and a significantly higher 81% in those who underwent TLND. 

Furthermore, quality of life data showed that the patients who only received the index LN procedure had significantly better physical, emotional, social and role functioning than those who underwent TLND, as well as a significantly higher score on the melanoma surgery subscale and a significantly lower level of fatigue. 

In addition, pain, insomnia, constipation and financial problems were all numerically lower among the patients who did not undergo TLND. 

“In summary, the PRADO trial confirms the high pathologic response rate and safety observed previously in OpACIN-neo”, Christian Blank concluded. 

Reference 

Blank CU, Reijers ILM, Pennington T, et al. First safety and efficacy results of PRADO: A phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma. J Clin Oncol 38: suppl; abstr 10002. DOI: 10.1200/JCO.2020.38.15_suppl.10002.