Experts released two important studies on the use of targeted therapy and immunotherapy in the metastatic melanoma scenario
During the virtual presentation of the AACR (American Association for Cancer Research), experts released two important studies on the use of targeted therapy and immunotherapy to treat metastatic melanoma. The studies were IMspire150 and SWOG S1320.
The first assessment results of atezolizumab (A), cobimetinib (C) and vemurafenib (V) in patients with previously untreated BRAF V600 metastatic melanoma were evaluated in the IMspire150, phase III, multicenter, randomized, double-blind, placebo-controlled trial, that was developed to assess the superiority of ACV compared to placebo + CV.
In the study, a total of 514 patients were randomized in a 1: 1 ratio stratified by geographic region and level of lactate dehydrogenase (LDH). It is important to mention, that despite patients in both groups started vemurafenib at 960 mg twice a day and cobimetinib at 60 mg once a day, the dosage of the first agent changed on day 22, which means, the dose of vemurafenib in the threefold scheme was reduced to 720 mg 2x / day. In cycle 2 onwards, atezolizumab or placebo was administered on days 1 and 15 every 28 days.
The primary endpoint of the study was progression-free survival (PFS) assessed by the investigator. The main secondary endpoints included PFS assessed by an independent review committee, objective response rate (ORR), duration of response (DoR) and overall survival (OS).
The study was positive in assessing progression-free survival, reaching a median of 15.1 months in the ACV group (95% CI, 11.4-18.4) vs 10.6 in the placebo group (95% CI, 9, 3-12.7; log-rank P = 0.0249). In addition, the median PFS, when assessed by an independent review committee, was 16.1 months (95% CI, 11.3-18.5) and 12.3 months (95% CI, 10.8-14.7) with ACV vs placebo + CV, respectively (log-rank P = 0.1607).
In the 12-month assessment, 54% vs 45.1% of patients remain alive in their respective groups. The response rate was comparable in both groups, around 65%. There was an increase in the median duration of response (21 months (95% CI, 15.1-non-assessable) vs 12.6 months [95% CI, 10.5-16.6]). The OS data is still immature, requiring more time for more accurate analysis.
The SWOG (Southwest Oncology Group) is part of the National Clinical Trials Network of the NCI (National Cancer Institute), which includes more than 2,000 cancer centers, university hospitals and community sites in the US and abroad. Using this network, SWOG S1320 registered 249 eligible melanoma patients at 68 places over a five-year period. From the 249 patients, 206 were randomized. Each patient received BRAF and MEK inhibitors combination regimens with dabrafenib and trametinib, respectively.
A group of patients (n = 105) received the combination daily until tumor progression. The other group (n = 101) received the same daily combination for five weeks, followed by a three-week break, returning to treatment for another five weeks, and so on until tumor progression.
The result showed that the patients in the continuous group had progression-free survival of 9 months vs 5.5 months in the intermittent group (HR, 1.36; 80% CI, 1.10-1.66; P = 0.063).
In the continuous group, 21 patients continued on treatment at the time of the analysis, with 84 patients who discontinued treatment, mainly due to disease progression (n = 54). In the intermittent group, 17 patients were still on treatment, with 84 who discontinued treatment, again mainly due to progression (n = 62).
Although the study was not designed to detect differences in overall survival (OS), there was no significant difference in observed survival, with an average OS of 29.2 months in each group.