Recently, the annual meeting of the American Society of Clinical Oncology (ASCO), which has a long reputation and global influence, was successfully held. This ASCO conference is rich in content, covering the latest progress of many tumor species, including gastric cancer, involving a large number of basic and clinical research, which is worth learning from scholars in the field of oncology.
At this year's ASCO conference, the results of the clinical study on single-drug chemotherapy combined with apatinib and PD-1 monoclonal antibody in the treatment of advanced gastric cancer, led by Professor Deng Ting of Tianjin Medical University Cancer Hospital, were officially announced. To this end, this journal specially invited Professor Deng Ting to interpret the results and significance of this research in detail, and look forward to its future development prospects, in order to convey the cutting-edge progress in the field of advanced gastric cancer to the majority of readers.
Professor Deng Ting
Cancer Hospital of Tianjin Medical University
Department of Gastroenterology, Cancer Hospital, Tianjin Medical University
Deputy Chief Physician Master Tutor
He is a member of the Clinical Research Committee of Tumor Drugs of the Chinese Anti-Cancer Association and the vice chairman of the Youth Committee
Member of the Tumor Support Treatment Committee of the Chinese Anti-Cancer Association
Member of the Chemotherapy Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of colorectal Cancer Committee of Beijing Society for Cancer Prevention and Control
Standing Member of the CSCO Youth Expert Committee
Fold the sand and press the armor
The road to second-line treatment options for patients with advanced gastric cancer has stagnated
Q1: As a treatment specialist in the field of gastric cancer, how do you view the current status of second-line treatment for advanced gastric cancer? What do you think are the unmet clinical needs of the moment?
Professor Deng Ting: At present, in China, the treatment of advanced gastric cancer is still based on single-drug standard chemotherapy modes such as paclitaxel and irinotecan. However, it is obvious that the above treatment methods are not effective, the effective rate is about 10%, and the overall PFS of patients is only 3 to 4 months, so there is an urgent need for new treatment options in the clinic to further improve the survival of second-line patients with advanced gastric cancer.
In 2010, the ToGA study confirmed that trastuzumab combined with chemotherapy can significantly prolong the overall survival of patients with HER2-positive metastatic gastric cancer, but for her2-negative gastric cancer patients, in the 10 years since then, despite continuous exploration, most of the well-known targeted drugs are in a state of collapse and sedimentation. Apatinib is the only approved anti-angiogenic drug for third-line and above indications for gastric cancer, and ramosumab has not yet been marketed in China. Until 2020, PD-1 monoclonal antibody began to see a new breakthrough in the first-line treatment of patients with HER2-negative advanced gastric cancer. However, if the dominant population is not selected, even if immune checkpoint inhibitors are added to the first-line treatment plan, the overall efficacy of the patient is still unsatisfactory, and for the failure of the first-line treatment, how to choose the second-line treatment plan is a treatment difficulty in the current clinical work. Therefore, for the treatment of patients with advanced gastric cancer, we still need to continue to explore.
It is reasonable and well-founded
The combination regimen is well designed
Q2: At the 2021 ASCO conference, the results of a clinical study of a single-agent chemotherapy combined with apatinib and PD-1 monoclonal antibody in the treatment of advanced gastric cancer were officially announced. In the context of the joint strategy in the field of oncology, why did you choose to apply the above combination of options?
Professor Deng Ting: At present, apatinib and PD-1 monoclonal antibody have been given third-line and above treatment indications for patients with advanced gastric cancer in China, but in actual clinical work, only 10% to 20% of patients can receive third-line treatment. Most patients are unable to continue treatment due to tumor progression and nutritional physical status before third-line therapy. Therefore, we hope to move the treatment time point of the third-line drug forward in order to achieve better efficacy of second-line treatment. In previous studies, anti-angiogenesis-targeted drugs combined with PD-1 monoclonal antibodies have demonstrated good coordination effects and are well tolerated and safe. At the same time, chemotherapy may also be a strategy for PD-1 monoclonal antibody combination therapy. The adverse reactions of chemotherapy are not significantly superimposed with these two categories. So we combined the three drugs as an option for back-line therapy.
Based on the above reasons, we have designed a second-line and above treatment regimen of single-agent chemotherapy combined with apatinib and PD-1 monoclonal antibody.
Reasonable, unexpected
The joint protocol study highlights the advantages of the backline forward medication
Q3: Can you please tell us more about the efficacy and safety data of this study? How would you rate the value of the study or its impact on actual clinical practice?
Professor Deng Ting: In fact, the preliminary results of the study were very unexpected. In this study, the patient's adverse reactions may come from three aspects: chemotherapy drugs, targeted drugs, and immune drugs, and surprisingly, there are fewer drug-related adverse reactions and the overall patient is well tolerated. The most common adverse events were leukopenia (61.5%), anemia (57.7%), neutropenia (53.8%), proteinuria (42.3%), hair loss (42.3%), hypothyroidism (38.5%), elevated alanine aminotransferase (34.6%), elevated aspartate aminotransferase (34.6%), but most were grade 1 or 2, and the most common grade 3 or 4 treatment-related adverse event was neutropenia (11.5%). I believe that the better safety of this regimen is due to the team's good full-process management of patients and dose control. However, the safe dose did not affect the final treatment effect, and the results of the study showed that 26 patients were currently enrolled (of which 4 were third-line to use the regimen), 24 were assessable, with ANR of 50%, DCR of 83.3%, median PFS of 7.06 months, and median OS had not yet been reached. This result has undoubtedly brought us a surprise and a good benefit for patients. Current enrollment is still in progress.
Keep improving and forge ahead
Innovation and exploration continue to work hard
Q4: Looking ahead, what are your research plans in the field of stomach cancer treatment? What is the progress so far?
Professor Deng Ting: After tumor treatment enters a new era of immunity, there is a "blowout" development trend in related research in the field of gastric cancer. At this year's ASCO conference, the phase II study on the use of immunocommunotherapy for neoadjuvant therapy for gastric cancer has initially shown a certain therapeutic effect, and the overall patient tolerance is good, of course, more phase III clinical studies are still needed to provide more high-level evidence-based medical evidence. In addition, the exploration of the therapeutic targets of gastric cancer is also endless.
The team is currently conducting a study of beat chemotherapy (low-dose capecitabine) combined with apatinib and carrelizumab for first-line treatment in patients with advanced gastric cancer. The main enrolled patients include two broad categories: those who are too old and infirm to tolerate conventional chemotherapy, and those who are completely reluctant to undergo chemotherapy. These populations are basically outside the admission criteria of conventional clinical research, but they are in our real world. We hope to explore the possibility that new protocols can benefit patients with "unconventional" advanced gastric cancer in the real world. Of course, it is also hoped that more centers can work together to solve problems in the clinic and benefit more patients.
Professor Deng Ting
Editors sorted out 丨 China Medical Tribune Can Be Sung