Editor's note: The annual meeting of the American Society of Clinical Oncology (ASCO), which has attracted global attention, was held in Chicago from May 31 to June 4 local time. As the world's most academic and influential clinical oncology conference, ASCO brings together the world's top experts and scholars to discuss and share the latest and most cutting-edge cancer research results. At the conference, we had the honor to interview Professor Guo Jun from Peking University Cancer Hospital to share the latest progress in the treatment of melanoma and look forward to future research directions. The content of the interview is now compiled and published for the benefit of readers.
Loading...
Oncology Watch: Can you tell us about the key developments in melanoma research at the 2024 ASCO Conference?
Prof. Jun Guo: In the oral presentation session of the just-concluded ASCO Annual Meeting, we witnessed a series of scientific milestones in the treatment of melanoma. These studies not only show the latest results in current treatments, but also point the way for the future treatment of melanoma.
First, as a key study at this year's ASCO Annual Meeting, the results of tumor-infiltrating lymphocyte (TIL) therapy combined with pembrolizumab for the first-line treatment of melanoma have attracted much attention [1]. The data showed that patients with advanced melanoma who received this therapy showed deep and durable clinical responses, with an objective response rate (ORR) of more than 60% and more than 20% of patients achieving complete response (CR). At present, there are also a number of TL-related studies in China, mainly for patients who are resistant to immune checkpoint inhibitors (ICIs) or have experienced multiple rounds of therapy.
After the introduction of TIL in combination with pembrolizumab in the first-line treatment of melanoma, we have seen that it still achieves high ORR and long progression-free survival (PFS). Although no final data on PFS have been obtained from this study, we can already see that the efficacy is already significant. Therefore, it is foreseeable that cellular immunotherapies such as TIL will advance rapidly in melanoma in the future and may lead the treatment direction of tumors.
Second, a three-drug regimen of LAG-3 in combination with PD-1 and CTLA-4 (ipilimumab) has also achieved positive results in the treatment of melanoma[2]. The study included a small number of patients with acral (4) and mucosal (3) melanoma, and the response was very good, with only one patient experiencing disease progression and the rest of the patients having tumor shrinkage.
In fact, many studies have been conducted in China on the regimen of LAG-3 plus PD-1 or PD-1 plus CTLA-4 in targeting mucosal and acral melanoma. However, we have not conducted a three-drug combination study, mainly because LAG-3 has not yet been approved for marketing in China. Therefore, the use of this three-drug combination regimen will be of great significance to patients with this special subtype of melanoma in the continental acral and mucosal regions, and we will continue to monitor the progress in this area, and look forward to more research data in the future to reproduce the positive efficacy of these 7 patients.
Oncology Outlook: Could you please introduce the latest results of the COMBI-AD study and its implications for clinical treatment?
Prof. Jun Guo: The COMBI-AD trial is a double-blind, placebo-controlled, randomized phase III study that aims to explore the efficacy and safety of dabrafenib (150 mg bid) + trametinib (2 mg qd) combination therapy compared with placebo for postoperative adjuvant therapy by including 870 patients with completely resected stage III cutaneous melanoma, including those with BRAFV600E/K mutations[3]. As early as the 2020 ASCO Annual Meeting, Professor Axel Hauschild, an international authoritative expert on melanoma, unveiled the 5-year follow-up data of this study, confirming that the adjuvant treatment regimen of dabrafenib + trametinib (D+T) can bring long-term benefits to patients.
At the annual meeting, Professor Axel Hauschild presented the latest data from the study, which evaluated the updated and final results of dabrafenib plus trametib in combination with placebo in patients with melanoma compared with placebo.
The data showed that the mean follow-up was 100.0 months in the D+T group and 82.5 months in the placebo group. The estimated RFS (HR: 0.52; 95%C1: 0.43~0.63) and DMFS (HR: 0.56; 95%C1: 0.44~0.71) both favored the dabrafenib plus trametinib group (Figure 1). Although patients in both the treatment and placebo groups did not achieve median overall survival (mOS; HR: 0.80; 95%CI: 0.62~1.01; P= 0.063) (Figure 2), but consistent OS benefit was observed in most of the prespecified subgroups (n=397; HR: 0.75; 95%CI: 0.58~0.96). The security profile is consistent with previous reports.
Fig.1 The trend of benefit in the RFS D+T group was better than that of placebo treatment
Fig. 2 Trend of OS benefit between the two groups
Overall, the COMBI-AD study provided the longest follow-up data (over 10 years) for adjuvant stage III melanoma to date. Treatment with dabrafenib in combination with trametinib significantly improved OS and reduced the risk of death by 20% in stage III melanoma compared to placebo. This indicates that dabrafenib combined with trametinib is currently the best choice for the adjuvant treatment of BRAF V600 mutant melanoma.
Oncology Monitor: Can you tell us about the breakthroughs in innovative therapies for melanoma at the 2024 ASCO Conference?
Prof. Jun Guo: At this year's ASCO conference, there was a significant trend of innovation in the treatment of melanoma. Among them, the oral report of a new drug study has attracted widespread attention. This study introduces a fusion protein that conjugates cytokines such as IL-2, IL-17, and TNF with antibodies, and uses intratumoral injection to provide a new therapeutic strategy for melanoma patients. Preliminary findings indicate that this innovative approach has already yielded positive results. For Asian patients, intramural injection of cytokines has a more far-reaching significance. Because of its potential to activate innate immunity, it is a boon for patients with acral and mucosal melanoma, which traditionally struggle to initiate an immune response. In the future, we will continue to make further explorations and attempts in this direction, in order to benefit more patients.
In addition, innovative explorations in the field of acral and mucosal melanoma research have also attracted attention. We noticed that every oral report of melanoma this year also clearly indicated whether or not acral or mucosal melanoma patients were included. Continental's research in this field is unique, and its outstanding achievements have led the global frontier, and attracted wide attention in the form of posters at the conference. These studies not only clarify the treatment effect, but also provide us with more possibilities for future treatment directions.
Not only that, in terms of innovative treatments, China's research has made remarkable progress in many aspects, such as oncolytic viruses, new immunotherapy models, and combination treatment regimens after immunotherapy failure. In particular, the three-drug combination regimen for acral melanoma has been followed up for a long time and the results have been encouraging. In the future, we look forward to making more breakthroughs in the fields of immunotherapy failure and new first-line cellular immunotherapy, and I firmly believe that we will deliver more wonderful answers in ASCO, contribute China's wisdom to the global melanoma treatment, and let the world listen to our Chinese voice."
Resources
[1]https://ir.iovance.com/news-releases/news-release-details/iovance-biotherapeutics-announces-clinical-data-frontline
[2]https://meetings.asco.org/2024-asco-annual-meeting/15784?presentation=233019#233019
[3] Long-term follow up for adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma: Final results of the COMBI-AD study.
Prof. Jun Guo
Peking University Cancer Hospital
Chief Physician, Doctoral Supervisor, Professor
Director of the Department of Melanoma and Sarcoma Medicine
Chief of the Department of Urological Oncology
Vice President and Secretary General of the Chinese Society of Clinical Oncology (CSCO).
Vice President of the International Melanoma Society (MWS).
President of the Melanoma and Skin Oncology Section of the European Oncology Congress (ESMO).
Chairman of the Melanoma Committee of the National Cancer Center and the National Cancer Quality Control Center
Chairman of the CSCO Melanoma Expert Committee
Vice Chairman of the CSCO Kidney Cancer Expert Committee
Vice Chairman of CSCO Immunotherapy Committee
Vice Chairman of CSCO Urothelial Carcinoma Committee
Vice Chairman of CSCO Prostate Cancer Committee
CFDA National Drug Registration Review Expert
Member of the Expert Committee on Rational Drug Use of the National Health and Family Planning Commission (Anti-tumor Drug Professional Group)