Breaking Ground in Gastric Cancer Treatment: Promising Phase 2 Trial Results for a Novel Combination Therapy
Study Overview
This study investigated the effectiveness of combining camrelizumab and apatinib with chemotherapy for the treatment of locally advanced gastric cancer (LAGC) (1). Conducted as a multicenter, randomized phase 2 trial (NCT04195828), this research explored a new approach in the treatment of gastric adenocarcinoma (clinical stage T2-4N+M0). The study design involved the random assignment of patients in a 1:1 ratio to two groups. One group received neoadjuvant camrelizumab and apatinib combined with nab-paclitaxel plus S-1 (CA-SAP), while the control group received the chemotherapy regimen SAP alone (SAP) for three cycles.
The study's primary endpoint was the major pathological response (MPR), defined as less than 10% residual tumor cells in resection specimens. Secondary endpoints included the R0 resection rate, radiologic response, safety, overall survival (OS), and progression-free survival (PFS). The analysis was based on a modified intention-to-treat population, comprising 51 patients in the CA-SAP group and 53 in the SAP group.
The results of the trial indicated that the CA-SAP regimen was associated with a significantly higher MPR rate of 33.3%, compared to 17.0% in the SAP group (P = 0.044). Furthermore, the CA-SAP group exhibited a higher objective response rate (66.0% vs. 43.4%, P = 0.017) and a higher R0 resection rate (94.1% vs. 81.1%, P = 0.042) than the SAP group. In terms of safety, nonsurgical grade 3-4 adverse events occurred in 33.3% of patients in the CA-SAP group and 26.4% in the SAP group.
The study concluded that the combination of camrelizumab and apatinib with chemotherapy as a neoadjuvant regimen was tolerable and associated with favorable responses in treating LAGC. However, it is noted that survival results were not reported due to immature data.
Standard Treatment
The current standard treatment for locally advanced gastric cancer (LAGC) typically involves a combination of chemotherapy, surgery, and sometimes radiation therapy. The specific regimen can vary based on factors such as the cancer's stage, location, the patient's overall health, and regional treatment guidelines. Commonly, chemotherapy is used either as neoadjuvant (before surgery) to shrink tumors and make them more operable, or as adjuvant therapy (after surgery) to eliminate remaining cancer cells. The chemotherapeutic agents used often include fluoropyrimidines (like 5-fluorouracil or capecitabine) and platinum-based drugs (like oxaliplatin or cisplatin).
The study in question, examining the combination of camrelizumab (a PD-1 inhibitor) and apatinib (an angiogenesis inhibitor) with chemotherapy, represents a novel approach. The use of immunotherapy (such as PD-1 inhibitors) and targeted therapy (like angiogenesis inhibitors) is a relatively recent development in gastric cancer treatment, primarily explored in advanced or metastatic settings.
The impact of this study's results can be considered significant for several reasons:
Enhanced Efficacy: The trial showed that the combination therapy led to higher rates of major pathological response and R0 resection, indicating more effective tumor reduction and potentially more complete surgical removal of the cancer.
New Therapeutic Options: The introduction of immunotherapy and targeted therapy in the neoadjuvant setting opens new avenues for treatment, which could be particularly beneficial for patients who may not respond well to standard chemotherapy.
Safety Profile: While the study reported higher rates of grade 3-4 adverse events in the combination therapy group, it was still considered tolerable. Understanding the safety profile is crucial for assessing the feasibility of new treatments.
However, several factors should be considered before deeming this new regimen as a replacement for current standards:
Phase of the Trial: This is a phase 2 trial, which means its primary goal is to assess efficacy and safety but in a relatively small patient population. Phase 3 trials, involving larger populations and often more diverse patient groups, are necessary to confirm these findings.
Long-term Outcomes: The trial did not report long-term outcomes such as overall survival and progression-free survival due to immature data. These outcomes are crucial for understanding the real-world impact of the treatment.
Generalizability: The results need to be replicated in broader and more varied patient populations to ensure that the findings are generalizable.
In conclusion, while the study presents promising results, further research in larger and more diverse populations, along with long-term outcome data, is necessary before this combination therapy can be considered as a new standard for treating LAGC.
Clinical Impact Potential
The clinical impact potential of this trial can be assessed as medium. This assessment is based on several key considerations:
Innovative Treatment Approach: The trial explores a combination of immunotherapy (camrelizumab) and targeted therapy (apatinib) with chemotherapy, which is a relatively novel approach in the treatment of locally advanced gastric cancer (LAGC). This represents a significant shift from the standard chemotherapy and could potentially address the unmet needs in LAGC treatment.
Promising Results: The trial demonstrated improved outcomes in terms of major pathological response, objective response rate, and R0 resection rate compared to chemotherapy alone. These results suggest a potential for better disease management and improved patient outcomes.
Safety and Tolerability: While the combination therapy showed a higher rate of grade 3-4 adverse events, it was still considered tolerable. The safety profile is a crucial factor in assessing the feasibility and acceptance of new treatments in clinical settings.
However, there are factors that moderate the potential impact:
Early Phase of Research: The study is a phase 2 trial, which, while indicative of efficacy and safety, requires further validation through phase 3 trials involving larger and more diverse populations to confirm these findings and establish real-world applicability.
Lack of Long-term Outcome Data: The trial did not report on long-term outcomes such as overall survival and progression-free survival, which are essential to fully understand the clinical benefits and impact of the treatment.
Specific Patient Population: The results are specific to patients with a certain stage of gastric cancer (clinical T2-4N+M0). The impact of this treatment on other stages or types of gastric cancer remains unknown.
In summary, the trial presents a medium clinical impact potential due to its innovative approach and promising early results, but this assessment is tempered by the need for further research to validate these findings in larger and more diverse populations, and to establish long-term benefits.
Reference
Lin JX, Tang YH, Zheng HL, Ye K, Cai JC, Cai LS, Lin W, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Zheng CH, Li P, Huang CM. Neoadjuvant camrelizumab and apatinib combined with chemotherapy versus chemotherapy alone for locally advanced gastric cancer: a multicenter randomized phase 2 trial. Nat Commun. 2024 Jan 2;15(1):41. doi: 10.1038/s41467-023-44309-5. PMID: 38167806; PMCID: PMC10762218.