Editor’s Note:
The 2023 European Society for Medical Oncology (ESMO) Annual Meeting was held in Madrid, Spain from October 20 to 24. The Oncology Frontier Reporting Team delved into the frontiers of international advancements, witnessing the progress of China’s anti-cancer efforts on the global stage. Professor Feng Wang from Sun Yat-sen University Cancer Center presented an important oral report at this conference. In an interview with “Oncology Frontier,” Professor Feng Wang shared insights into two studies and highlights in the field of gastric cancer at the ESMO conference. This issue compiles relevant content for readers.
Oncology Frontier: Due to the impact of the pandemic, domestic experts had face-to-face exchanges with international scholars at the ESMO venue for the first time in several years. Could you share your feelings about attending this conference and any impressive research developments?
Professor Feng Wang : Hello to all online friends! I am Dr. Feng Wang from the Internal Medicine Department of Sun Yat-sen University Cancer Center. I am delighted to be back at the ESMO Annual Meeting after several years and meet everyone again. This year, led by Professor Xu Ruihua, the Digestive Tumor Internal Medicine team from Sun Yat-sen University Cancer Center brought six oral presentations covering the latest research progress from the esophagus to the stomach to the intestine.
At the ESMO venue, we heard about the latest developments in gastrointestinal tumors, such as the KEYNOTE-585 study comparing chemotherapy combined with immunotherapy versus chemotherapy for neoadjuvant therapy in gastric/esophagogastric junction cancer and the KEYNOTE-811 study comparing immunotherapy combined with trastuzumab and chemotherapy versus trastuzumab combined with chemotherapy for HER2-positive metastatic gastric/esophagogastric junction adenocarcinoma. These results showed that the combination of immunotherapy achieved better efficacy in neoadjuvant therapy for gastric cancer and first-line treatment for metastatic gastric cancer.
In June of this year, our team reported a study on neoadjuvant treatment of resectable gastric cancer with immunotherapy combined with chemotherapy versus chemotherapy alone at the American Society of Clinical Oncology Annual Meeting. The results showed that the pathological complete response rate in the immunotherapy group was about three times higher than that in the chemotherapy group. Professor Kohei Shitara’s KEYNOTE-585 study also demonstrated a significant increase in pathological complete response rate (10.9% improvement) and a substantial improvement in event-free survival (44.4 vs. 25.3 months) in the immunotherapy group. Although the predefined p-value was very small and did not reach statistical significance, the improvement in event-free survival is clinically meaningful.
Professor Yelena Y. Janjigian’s KEYNOTE-811 study showed that in HER2-positive gastric cancer patients, the immunotherapy group, compared to the standard treatment group, significantly increased the objective response rate (72.6% vs. 59.8%), median progression-free survival (10.0 vs. 8.1 months), 24-month PFS rate (27% vs. 13%), and median duration of response (11.2 vs. 9.0 months). Overall survival data are not yet mature. Subgroup analysis showed significant differences in objective response rate and progression-free survival in patients with PD-L1 CPS≥1 but not in those with PD-L1 CPS＜1, suggesting that CPS scoring may predict the benefits of immunotherapy not only in the overall population but also in the HER2-positive population.
Oncology Frontier: You reported on a Phase II clinical trial (Abstract No. 556MO) investigating the efficacy of Sintilimab combined with Apatinib with or without Bevacizumab in the treatment of MSS/pMMR metastatic colorectal cancer. Could you discuss the background, design, and main results of this study?
Professor Feng Wang : This year, I presented a Phase II multicenter, open-label study led by our team, evaluating Sintilimab combined with Apatinib and Bevacizumab (three-drug group) compared to Sintilimab combined with Apatinib (two-drug group) as third-line or later treatment for MSS/pMMR metastatic colorectal cancer (Abstract No. 556MO). For microsatellite stable (MSS/pMMR) colorectal cancer, the efficacy of single-agent immunotherapy is less than 5%. We conducted extensive explorations, including PD-1 antibody combined with regorafenib and PD-1 antibody combined with apatinib. Although these results showed an increased efficacy rate of around 10%, most patients still did not achieve very good results, and progression-free survival (PFS) was only 1.5 to 2 months. In preclinical studies, we explored the combination of HDAC inhibitor Apatinib with PD-1 antibody and anti-angiogenesis drugs, and found a very good synergistic effect, leading to this Phase II clinical trial.
A total of 48 patients who had received at least second-line treatment for chemotherapy-failed or intolerant MSS/pMMR metastatic colorectal cancer were enrolled and randomly assigned to two groups. The objective response rate (ORR) in the three-drug group was 44%, disease control rate (DCR) was 72.0%, and median PFS was 7.3 months, while the ORR in the two-drug group was 13%, DCR was 39.1%, and median PFS was 1.5 months. The hazard ratio (HR) for the risk of death in the three-drug group compared to the two-drug group decreased significantly in all subgroups. Overall survival data are not yet mature, so it is unknown whether there is a significant improvement in OS, but we are eagerly awaiting the results. These results are not only seen in colorectal cancer but also in animal models of other tumors, showing very promising prospects. We hope that the combination of HDAC inhibitors with PD-1 inhibitors and anti-angiogenesis drugs can achieve significant efficacy in multiple tumor types, and the research results will be presented soon, possibly bringing new treatment options for patients with solid tumors such as colorectal cancer.
Oncology Frontier: Could you share the main results of another study you reported on, the AdvanTIG-203 study (Abstract No. 1020MO), which investigated the use of Camrelizumab combined with Toripalimab in the treatment of PD-L1-positive esophageal squamous cell carcinoma?
Professor Feng Wang: I also reported on a multicenter, randomized Phase II AdvanTIG-203 study evaluating the use of Camrelizumab combined with Toripalimab as second-line treatment for unresectable locally advanced or recurrent, metastatic PD-L1-positive esophageal squamous cell carcinoma (Abstract No. 1020MO). This study was conducted in 60 centers, including 46 Asian centers and 14 European centers, with a total of 125 patients. One group received the PD-1 antibody Toripalimab combined with placebo, the traditional second-line standard treatment, and the other group received Toripalimab combined with the TIGIT antibody Camrelizumab. The results showed that there was no significant difference between the two groups in terms of efficacy and safety. Numerically, there was about a 10% significant difference in the investigator-assessed ORR between the two groups (30.6% in the Camrelizumab group vs. 20.6% in the placebo group), but due to sample size issues, there was no statistical difference between the two groups. There was also no significant difference in PFS and ORR assessed by the independent evaluation committee. Overall survival data are not yet mature, with less than 50% of the expected OS data available, requiring further follow-up. The incidence of grade 1-4 or grade 3 and above adverse events in both groups was similar, with no significant difference in safety.
