Yifan Zhang, Tong Xie, Zhi Peng, Lin Shen (Department of Digestive Oncology, National Key Laboratory of Integrated Prevention and Treatment of Digestive Tumors, Beijing Key Laboratory of Translational Research in Malignant Tumors, Peking University Cancer Hospital and Beijing Institute of Cancer Prevention and Treatment, Beijing 100142, China)
Corresponding author: Shen Lin
E-mail:[email protected]
Prof. Lin Shen
Chief physician, professor and doctoral supervisor
Director of the Department of Digestive Oncology and Director of Phase I Clinical Trial Ward, Peking University Cancer Hospital
Beijing Scholar
Beijing Outstanding Contribution Expert
Chairman of the Tumor Precision Therapy Professional Committee of the Chinese Anti-Cancer Association
The first chairman of the Clinical Research Committee of Cancer Drugs of the Chinese Anti-Cancer Association
Chairman of the Clinical Research Expert Committee of the Chinese Society of Clinical Oncology
He is the chairman-designate of the Gastric Cancer Expert Committee of the Chinese Society of Clinical Oncology
She is the chairman of the Clinical Oncology Committee of the Chinese Women Physicians Association
Editor-in-chief of the Electronic Journal of Comprehensive Oncology Therapy
【Abstract】As a disease with the highest incidence and mortality rate of malignant tumors in China, gastric cancer has the characteristics of high heterogeneity and poor prognosis, and its drug treatment has always been a difficult point in medical research. In recent years, with the development of immunotherapy and targeted therapy, gastric cancer treatment has gradually developed in the direction of precision, and has gradually grown in setbacks. This article reviews the current status and existing problems of gastric cancer treatment in 2023, with special attention to the latest advances in perioperative therapy, immunotherapy and targeted therapy.
【Keywords】gastric cancer, perioperative treatment, immunotherapy, targeted therapy
Gastric cancer (GC) is one of the most common malignant tumors in China, which is highly aggressive and heterogeneous, and seriously threatens the life safety of patients. In recent years, with the development of immunotherapy and targeted therapy, GC therapy has gradually developed in the direction of precision, which has improved the survival and prognosis of patients with advanced gastric cancer, but there are still some challenges and unsolved problems, this article intends to summarize the current situation and existing problems in the field of GC in 2023, focusing on the latest progress in perioperative therapy, immunotherapy and targeted therapy.
1. Perioperative treatment: opportunities and difficulties coexist
The role of perioperative therapy in advanced GC is widely recognized. At the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, the RESOLVE study was presented with its latest 5-year follow-up results: the perioperative SOX regimen (oxaliplatin plus Tigio) significantly improved the 5-year survival rate of patients with locally advanced GC (60.0% vs. 52.1%) compared with adjuvant postoperative XELOX regimen alone (oxaliplatin plus capecitabine) , HR=0.79, 95%CI 0.62~1.00) and 5-year disease-free survival (DFS) rate (53.2%vs. 45.8%, HR=0.79, 95%CI 0.63~0.98), and can reduce the risk of death by 21%[1]. This reaffirms that perioperative SOX therapy can improve patient survival and is a superior choice for neoadjuvant chemotherapy in patients with locally advanced GC.
With the gradual advancement of immunotherapy to front-line treatment, clinical trials of perioperative immunotherapy for GC are in full swing, and a number of clinical studies have observed a significant increase in pathologic complete response (pCR) rate. The results of the perioperative study of toripalimab combined with chemotherapy presented at the 2023 American Society of Clinical Oncology (ASCO) annual meeting showed that compared with chemotherapy alone, the proportion of tumor regression grading (TRG) 0/1 in the immunotherapy group increased from 20% to 44%, and the pCR rate also increased from 9.3% to 24.1%[2]. In a similar PERSIST study, the pCR rate was 26.9 and 4.8 percent in the sintilimab arm and 4.8 percent in patients treated with SOX alone and 69.2 and 28.6 percent in major pathologic response (MPR), respectively [3]. In the DANTE study, a significant benefit was observed in both pathological de-staging and pathologic remission with atezolizumab in combination with FLOT (fluorouracil + leucovorin + oxaliplatin + docetaxel) [4]. The phase III MATTERHORN study evaluated the efficacy and safety of the programmed cell death ligand 1 (PD-L1) monoclonal antibody durvalumab in combination with FLOT in the perioperative treatment of patients with resectable GC and gastroesophageal junction cancer (GEJC). Durvalumab combined with FLOT chemotherapy also improved the pCR rate (19% to 7%), but long-term survival data need to be further updated [5].
The KEYNOTE-585 study is the first global phase III clinical trial of GC with survival follow-up data to evaluate the efficacy of pembrolizumab in combination with chemotherapy as a perioperative treatment for locally advanced GC and GEJC [6]. The study set two primary endpoints, namely pCR rate and event-free survival (EFS), and compared with chemotherapy alone, the addition of pembrolizumab resulted in a significant short-term pathologic response (pCR rate 12.9% vs. 2.0%, P<0.000 1) and an R0 resection rate of 80% Long-term survival showed a trend of benefit (EFS 44.4 months versus 25.3 months, HR=0.81, P=0.019 8), and the addition of pembrolizumab did not increase serious adverse reactions, with the incidence of grade 3 treatment-related adverse events in the immunotherapy combination group and placebo group ≥ 65% and 63%, respectively.
Immunotherapy has achieved good short-term efficacy in the field of neoadjuvant therapy for GC, such as significant improvement in pCR and significant down-staging, but there is still a lack of evidence that the long-term survival benefit meets the purpose of statistical design, and longer follow-up or other trial results are needed. In-depth exploration of biomarkers may help in accurate patient screening and treatment optimization. In addition, the choice of different immune checkpoint inhibitors and the new exploration of combination therapy regimens may also be key factors affecting the efficacy of perioperative therapy. Results from the Dragon-IV/Ahead-G208 study suggest that apatinib + camrelizumab + SOX chemotherapy regimens achieved a significant increase in pCR compared with chemotherapy alone, with a pCR rate of 18.3% in the targeted therapy + immunotherapy + chemotherapy combination therapy group compared with 5% in the chemotherapy alone group [7]. Another phase II study also evaluated camrelizumab + apatinib + S-1 ± oxaliplatin for the treatment of locally advanced cT4a/bN+ GC [8] and showed a pCR of 15.8 percent and 26.3 percent, respectively, in the no-oxaliplatin versus oxaliplatin plus groups. Multiomic analysis revealed several potential biomarkers, including RREB1 and SSPO mutations, immune-related features, and peripheral T cell expansion scores, and explored the dynamics of the immune microenvironment, dominant tumor subcloning, and T cell receptor repertoire during neoadjuvant immunotherapy. These data need to be further validated in large randomized trials.
The ATTRACTION-5 study, the first phase III clinical trial to evaluate immunotherapy in combination with chemotherapy in combination with the adjuvant treatment of the phase III gastric or gastroesophageal junction, failed to meet the primary endpoint of recurrence-free survival (RFS) [9]. The study enrolled 755 patients who were randomized 1:1 to receive nivolumab (nivolumab group) and placebo in combination with SOX (oxaliplatin and tigio) or XELOX (oxaliplatin and capecitabine) as adjuvant therapy (placebo group), and the 3-year RFS rates in the nivolumab group and placebo group were 68.4% and 65.3%, respectively (HR=0.90, 95%CI 0.69~1.18). In this study, the proportion of PD-L1 positive people was only about 13%, which was much lower than the real-world proportion, and in the RFS subgroup analysis, some people tended to benefit from immunotherapy combined with adjuvant chemotherapy, such as the Eastern Cooperative Oncology Group activity status score of 1 point, pathological stage III.C, and PD-L1 tumor cell positive proportion score of ≥1%. This means that treatment with programmed cell death protein 1 (PD-1) inhibitors may be of great value in patients with positive PD-L1 expression. This study also has reference significance for follow-up studies to screen the immune benefit population, and also makes people look forward to the data of the phase III study (NCT05180734) of toripalimab combined with chemotherapy as an adjuvant regimen for GC in Chinese populations. In the EORTC 1707 VSTIGE study, which explored adjuvant dechemization, the double-immune group did not improve the duration of DFS compared with the chemotherapy group (11.9 months versus 23.3 months) [10]. This suggests that the role of chemotherapy in the adjuvant treatment of GC is not irreplaceable.
THE RESULTS OF THE GERCOR NEONIPIGA [11] AND INFNITY [12] STUDIES SHOWED THAT PATIENTS WITH MICROSATELLITE INSTABILITY (MSI-H) GC WERE TREATED WITH PD-1 AND PD-L1 INHIBITORS COMBINED WITH CYTOTOXIC T-LYMPHOCYTE ASSOCIATED PROTEIN 4 4, CTLA-4) after double immunization therapy reached 59% and 60%, respectively, confirming the strong anti-tumor efficacy of double immunization therapy in the treatment of GC patients with MSI-H. Although two studies validated the efficacy of neoadjuvant immunotherapy in this patient population, the clinical stage (cT2~3, N0~1) of the patients included in the GERCOR NEONIPIGA study was early, and the pCR rate of patients with T4 disease in the INFNINY study was only 17%, while the pCR rate of patients with T2~T3 was close to 90%. The stability of dual-immunity therapy still needs to be verified by larger clinical samples.
2. Research progress in the treatment of advanced GC
2.1 Advances in first-line immunotherapy
Data from multiple phase III clinical studies, such as CheckMate-649, ORIENT-16, RATIONALE 305, KEYNOTE-859, and GEMSTONE-303, provide solid evidence for first-line immunotherapy for advanced GC. Together, these studies have shown that the combination of PD-1 inhibitors in addition to standard first-line chemotherapy can significantly improve the survival of patients with advanced GC, which has been accepted by international guidelines and included in the first-line standard treatment regimen for advanced GC, among which the CheckMate-649 study is a landmark clinical trial that officially opens the immune era of GC therapy. At the 2023 ASCO Annual Meeting, the 3-year overall survival (OS) rate of nivolumab + chemotherapy was 31%, nearly three times that of the chemotherapy group (11%) in Chinese patients with a PD-L1 combined positive score (CPS) of ≥5 ), which established the standard position of immunotherapy in the first-line of advanced GC [13], and the objective response rate (ORR) of nivolumab combined with chemotherapy was nearly 20% higher than that of chemotherapy, and the duration of response (DOR) was > in both the whole population and the PD-L1 CPS≥5 populationAt one year, the median progression-free survival (PFS) time in the Chinese subgroup was nearly 1.5 times longer than that of chemotherapy (8.3 months vs. 5.6 months), and the median PFS time in the CPS≥5 population was nearly doubled compared with chemotherapy (8.5 months vs. 4.3 months), reflecting the unique "tailing effect" of immunotherapy. The subgroup analysis of the study showed that the median OS time of patients who achieved complete response (CR) and partial response (PR) within 18 weeks of treatment could be as long as 21.5 months, suggesting that patients with deep tumor shrinkage are the people who benefit from long-term survival, which brings more enlightenment to clinical practice. Similarly, long-term follow-up data from the ORIENT-16 study were presented at the 2023 annual meeting of the American Association for Cancer Research (AACR) [14]. A total of 650 subjects were included in the study, with a median follow-up time of 33.9 months, and the final analysis results showed that sintilimab combined with chemotherapy significantly reduced the risk of death in the CPS≥5 population and the overall population, among which the median OS time of patients with PD-L1 CPS≥5 was extended by 6.3 months (19.2 months vs. 12.9 months), and the median OS time in the overall population was extended by 2.9 months (15.2 months vs. 12.3 months); The 3-year OS rates were 37.6% and 26.0%, respectively, and the 2- and 3-year OS rates in the CPS≥5 population were 43.6% and 29.0%, respectively. In the GEMSTONE-303 study, sugemalimab plus ≥chemotherapy significantly improved PFS (7.6 months versus 6.1 months) and OS time (15.6 months versus 12.6 months) and ORR by 15.9% (68.6% versus 52.7%) compared with placebo plus chemotherapy [15]. Sugemalimab has also become the world's first PD-L1 inhibitor to succeed in the field of GC and GEJ.
In these studies, although immunotherapy combined with chemotherapy showed a survival benefit in the whole population, the benefit was more significant in the PD-L1 expression positive population. Data from the RATIONALE 305 study showed that tislelizumab combined with chemotherapy significantly extended the median OS time (17.2 months vs. 12.6 months, 95% CI 0.59~0.94) and median PFS time (7.2 months vs. 5.9 months, 95%) of PD-L1 tumor area positivity score (TAP) ≥ 5.5% (95%) and median PFS time (7.2 months vs. 5.9 months, 95% The CI was 0.55~0.83), and it could improve the ORR (50.4%vs. 43.0%) and median DOR (mDOR) (9.0 months: 7.1 months). This regimen has been included in the 2023 Chinese Society of Clinical Oncology (CSCO) GC guidelines and listed as a Class I.A recommendation [16]. Results from the KEYNOTE-859 study showed that chemotherapy plus pembrolizumab prolonged OS by only 1.5 and 1.6 months in the overall population and in the PD-L1 CPS≥1 population, and nearly four months in the PD-L1 CPS≥10 population [17]. According to the results of a number of clinical studies, the response of patients to immunotherapy is closely related to PD-L1 expression, and the higher the expression level, the more obvious the OS benefit trend, while the PD-L1 negative population is difficult to benefit. In current clinical practice, the detection of PD-L1 expression has not been fully unified, and both CPS calculated by cell counting and TAP evaluated based on visual image analysis have been considered in many studies, and the consistency between the two has been preliminarily verified in small sample studies [18]. The immune microenvironment of GC is complex, and the expression of PD-L1 is not the only predictor of efficacy. In the future, it is still necessary to continue to explore the characteristics of GC immune microenvironment and screen potential therapeutic beneficiaries by combining multiple markers.
2.2 Dual-immune therapy is expected to further expand the population benefiting from immunotherapy
Cadonilimab (AK104) is the world's first PD-1 and CTLA-4 bispecific antibody to enter clinical trials, and has demonstrated good efficacy and safety in early trials [19]. In 2023, the 2-year follow-up data of the phase II clinical study of cadonilimab combined with chemotherapy for the first-line treatment of GC, GEJC-I.b, and II were updated, and the data results continued the previous efficacy: the median OS time in the whole population was 17.41 months, the median PFS was 9.2 months, the 12-month OS rate was 61.4%, the ORR was 68.2%, and the disease control rate (DCR) was 92%, and the PD-L1 was high In the CPS≥5 population, the median OS duration was as high as 20.24 months [20]. Among real-world patients with advanced GC in China, the proportion of patients with low PD-L1 expression (CPS 1~4) or negative expression (CPS<1) is about 13 percent and 38 percent, respectively, which is more than 50 percent of the total patient population [21]. At present, the OS and PFS benefits of PD-1 inhibitors combined with chemotherapy as first-line therapy for these patients are still relatively limited, with a median OS time of 10~12 months, but in this phase II study, AK104 combined with chemotherapy still showed outstanding efficacy in patients with low PD-L1 expression or negative PD-L1. In this trial, >50% of the PD-L1 expression-negative (CPS<1) population and only 15% of the PD-L1 high-expression population (CPS≥5) were enrolled, and the median OS time and median PFS time of PD-L1 CPS<1 population were 17.64 months and 8.18 months in the subgroup analysis. This suggests that the emergence of dual-immune drugs is expected to bring more efficient clinical treatment methods for such patients, and it is particularly worth looking forward to whether such dual-immune therapy is better than the previous first-line treatment of PD-1 and PD-L combined with chemotherapy. Recently, the Phase III clinical trial (AK104-302) of AK104 in combination with XELOX chemotherapy for the first-line treatment of advanced GC and GEJC also announced that its interim analysis met the primary endpoint (OS), and the relevant data are yet to be disclosed.
2.3 Exploration of precision immunotherapy for special populations
As a specific subtype of GC, GC of MSI-H has historically been regarded as the dominant population for immunotherapy. KEYNOTE-061, KEYNOTE-062 and other studies have demonstrated a high response rate of immunotherapy in GC patients with MSI-H. Results from the KEYNOTE-158 study in China were reported at the 2023 ESMO Annual Meeting, with an ORR of 70% and a 12-month DOR rate of 85.7%, reaffirming the durable antitumor activity of pembrolizumab in Chinese patients with advanced microsatellite instability-high (MSI-H) solid tumors [22].
The exploration of the dual-free treatment mode for GC patients with MSI-H is also ongoing. The preliminary results of the NO LIMIT study showed that the ORR of nivolimum combined with ipilimumab for first-line treatment of GEJC patients with advanced GC and MSI-H was 62.1% (95%CI 42.3~79.3), of which 3 patients (10%) achieved CR, DCR was 79.3% (95%CI 60.3~92.0), and the median PFS time was 13.8 months (95% The CI was 13.7~not reached), and in terms of safety, it was consistent with the known safety spectrum of double free therapy [23]. In the CheckMate 649 biomarker analysis, a high proportion of Treg cells, a high number of chemokines, and a low proportion of fibroblasts and endothelial cells were associated with longer survival in patients who were immunotherapy [24]. The clinical utility of these biomarkers needs to be further prospectively verified.
3、人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）阳性GC治疗进展
After 10 years of inactivity, the KEYNOTE-811 study combined anti-PD-1 and anti-HER2 therapy with chemotherapy and made progress in the treatment of HER2-positive GC: the first interim results showed an ORR of 74.4% in the combination group, and in the second interim analysis, pembrolizumab combined with chemotherapy achieved a significant improvement in PFS time compared with trastuzumab plus chemotherapy (median PFS 10.0 months versus 8.1 months, HR = 0.72, 95% CI 0.60~0.87), PFS was prolonged by 3.6 months (median PFS 10.8 months vs. 7.2 months; HR=0.70, 95%CI 0.58~0.85) and the risk of disease progression was reduced by 30% in the subgroup of patients with PD-L1 CPS≥1 [25]. At the follow-up to 38.5 months, the median OS time of the pembrolizumab combination group was 20.0 months, and the median OS time of the targeted combination chemotherapy group was 16.8 months (HR=0.84, 95%CI 0.70~1.01), which did not meet the primary endpoint of significantly prolonged OS time<. 5 months, HR=1.03, 95%CI 0.65~1.64), OS time was even worse than that of the control group (median OS time was 16.1 months versus 22.3 months, HR=1.61, 95%CI 0.98~2.64).
Based on the results of the positive study of the domestic drug vedicitumab in patients with HER2-positive GC in the third line and above, in 2023, CSCO updated the third-line targeted therapy regimen for HER2-positive GC and moved vedicitumab forward from the level II recommendation to the level I recommendation. The DESTINY-Gastric06 study evaluated the efficacy and safety of DS-8201 monotherapy in Chinese patients with HER2-positive advanced GC who had received ≥ second-line therapy, with an ORR of 28.8% and median OS, PFS and mDOR of 10.2 months, 5.7 months, and mDOR of 7.9 months, respectively. DS-8201 is expected to provide a more effective individualized treatment regimen for HER2-positive patients in mainland China [26].
In the process of continuous research and development of new anti-HER2 drugs, combination therapy strategies have also been continuously explored. Zenidatumab is a bispecific antibody that simultaneously targets two nonoverlapping epitopes of HER2. In the phase I.b/II study of zenidatumab in combination with tislelizumab and chemotherapy in patients with HER2-positive advanced GC and GEJC, the overall population ORR was 75.8 percent, including 1 patient achieving CR, 24 achieving PR, and 8 patients achieving stable disease with a DCR of 100 percent, with a median PFS of 16.7 months and an mDOR of 22.8 months [27]. This suggests that the combination of zenidatumab in combination with chemotherapy and immunotherapy is expected to produce significant and sustained efficacy. In addition, camrelizumab in combination with pyrotinib and chemotherapy has shown promising efficacy in the first-line treatment of HER2-positive GC and GEJC, with ORR and DCR of 96.0 and 100 percent, respectively [28]. In advanced HER2-positive GC or solid tumors SHR6390 pyrotinib combined with ORR and DCR were 50.0 and 93.8 percent, respectively, with a median PFS of 3.88 months (95% CI 3.59~4.17) and a median OS of 12.48 months (95% CI 3.82~21.1) [29]. This has shown encouraging efficacy. As more and more drugs are put into clinical use, clinicians need to be cautious in drug selection, combination therapy consideration, and treatment strategy development while maintaining a positive attitude.
4. Progress in targeted therapy of Claudin 18.2 protein
Claudin 18.2 is a transmembrane protein found in normal gastric cells, which is the main component of the tight junction between the epithelium and endothelium, controls the molecular flow between cells, and can be expressed in the normal mucosa of the stomach, and is gradually exposed to the cell surface with the development of GC, making it an excellent target for GC treatment. Recently, two phase III studies, SPOTLIGHT [30] and GLOW [31], evaluated the efficacy and safety of zotuximab in combination with mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) or XELOX in the treatment of CLDN18.2 (Claudin-18 splice variant 2)-positive, HER2-negative advanced GC, respectively, showing a significant increase in PFS and OS time, confirming the great potential of targeted CLDN18.2 therapy. In the SPOTLIGHT study, zotuximab plus mFOLFOX6 was beneficial in both the median PFS time to the primary endpoint (10.61 months vs. 8.67 months, HR=0.751, 95%CI 0.589~0.942) and the median OS time to the secondary endpoints (18.23 months vs. 15.54 months, HR=0.750, 95%CI 0.60~0.94). In the GLOW study, zotuximab + XELOX treatment showed similar clinical outcomes to the SPOTLIGHT study, with median PFS time (8.21 months vs. 6.80 months, HR=0.687, 95%CI 0.540~0.867) and median OS time (14.39 months vs. 12.16 months, HR=0.771, 95%CI 0.62~0.97) both groups prolonged, and the ORR was 53.8% and 48.8%, respectively. The preliminary results of monoclonal and bispecific antibody drugs in the TST001 [32], ZL-1121 [33], MIL93 [34], and Q-1802 [35] studies also add evidence for CLDN18.2 as a target. It is worth noting that since Claudin 18.2 is also expressed in the normal gastric mucosal epithelium, the impact of adverse drug reactions on patient compliance and whether antibody-drug conjugate (ADC) drugs will aggravate normal mucosal injury should also be considered.
Claudin18.2-chimeric antigen receptor T-cell immunotherapy has shown preliminary efficacy in phase I clinical studies of advanced GC, with ORR and DCR of 57.1% and 75.0%, respectively, and a 6-month OS rate of 81.2% in GC patients. However, there are urgent issues to be solved regarding the impact of tumor heterogeneity, tumor suppression microenvironment on efficacy, safety management, and high treatment costs, and follow-up phase II.~III clinical studies are underway.
With the continuous innovation of ADC technology, the ADC drug exploration and innovation of CLDN18.2 is also booming. SYSA1801 has demonstrated good early anti-tumor efficacy in patients with advanced malignant solid tumors expressing CLDN18.2 [36], and phase I studies such as CMG901 have also shown preliminary results [37]. Exploring the joint exploration of CLDN18.2 ADC drugs and immunotherapy has also become a hot direction in the future, and related clinical studies are ongoing. However, at present, the development of drugs targeting CLDN18.2 is mostly based on immunohistochemistry, and there are differences in the detection antibodies, platforms, and patient population criteria used in different studies, and there is a lack of unified CLDN18.2 detection and interpretation standards. In addition, although ADC drugs have brought significant benefits to GC patients, their unique resistance mechanisms are also being explored, including downregulation of cell surface antigens, impaired drug efflux proteins, endocytosis, defects in internalization pathways (e.g., AKT signaling), overexpression of transporters, and lysosomal degradation. At present, the research on the mechanism of ADC resistance in GC is still limited to preclinical models, and needs to be more widely explored in future clinical treatments.
In the current therapeutic field of advanced GC, biomarker-driven precision targeted therapy has become a research trend. In addition to HER2 and Claudin 18.2, clinical trials for new targets such as FGFR2 [38], cMET, TROP2, DKK1, and PIK3CA are still in full swing, and more positive results are being reported.
5. Summary
In the field of GC drug research, there have been decades of constant challenges, setbacks, but still continue to struggle. The positive results of KEYNOTE-859, GEMSTONE-303, KEYNOTE-811 and other studies in 2023 further confirmed the effectiveness of immunotherapy in HER2-positive and negative GC, broadened the corresponding indications, and changed the choice of clinical practice. Comprehensive, dynamic assessment. The specificity and sensitivity of conventional PD-L1 and tumor mutational burden in predicting GC immune efficacy still need to be improved, and emerging omics technologies need to be optimized. With the positive results of the two phase III studies of SPOTLIGHT and GLOW, the approval of the Claudin 18.2 target is imminent, and the treatment options for advanced GC will be increased soon, but how to further screen the beneficiary population and the lineup of late-line drugs still need to be further explored. New anti-ADC drugs represented by DS-8201 and RC48 are gradually emerging, and the continuous iteration of drug research will surely bring new benefits to GC patients. "Precision" has become the inevitable direction of future drug research and development, whether it is the exploration and integration of new mechanisms of existing targets, or the study of niche targets, it is necessary to continue to dig deeper and accurately design. In the future, we will continue to move forward in the exploration to provide more options for drug treatment and regimens for GC patients and improve their clinical outcomes.
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