Stomach (Gastric) Cancer- Part 2

In part 2 of our stomach cancer blog, we will dive into the current treatment options for stomach cancer. We will also look at the recent advancements and new strategies being developed and how they are improving treatment outcomes for patients.

Current treatment strategies

The treatment of stomach cancer is guided by the cancer's stage, location, and the patient's overall health. For early-stage cases, surgery remains the primary curative approach. Depending on the tumor's extent, surgical options include endoscopic mucosal resection (EMR) for cancers confined to the stomach lining or gastrectomy (partial or complete removal of the stomach). In more advanced cases, surgery is often combined with other therapies to improve outcomes.

Chemotherapy is a critical component of stomach cancer treatment and may be administered either as a neoadjuvant therapy (before surgery) to shrink tumors or as an adjuvant therapy (after surgery) to reduce recurrence risk and improve survival. The standard chemotherapy regimen for stomach cancer is FLOT (Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel). However, for patients unable to tolerate FLOT, alternative regimens such as CAPOX (Capecitabine and Oxaliplatin) or FOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin) may be considered. In metastatic cases, chemotherapy often involves fluoropyrimidines combined with platinum-based drugs.

Radiotherapy is another important modality, particularly for locally advanced or unresectable cancers. It may be used post-surgery to reduce the risk of recurrence or palliatively to alleviate symptoms in advanced stages. Combining radiotherapy with chemotherapy enhances its effectiveness, as chemotherapy acts as a radiosensitizer, improving the impact of radiation. Studies have demonstrated that the addition of radiotherapy to surgery significantly reduces local recurrence rates—for instance, from 27% with surgery alone to 10% with combined therapy. Radiotherapy also improves surgical outcomes by increasing the likelihood of R0 resections (complete removal of the tumour). Furthermore, the combination of radiotherapy and chemotherapy has shown promise in improving both disease-free survival and overall survival.

For patients with advanced or unresectable stomach cancer, treatment focuses on symptom relief and enhancing quality of life. Supportive interventions may include stent placement to relieve blockages or laser therapy to reduce tumour burden and alleviate symptoms.

Recent treatment advances

Innovative therapies and advancements in stomach cancer treatment have significantly improved patient outcomes, introducing new drugs, refined surgical methods, and personalized approaches. These developments are shaping the landscape of gastric cancer management and providing hope for improved survival and quality of life.

Targeted Therapies

One of the most groundbreaking developments in stomach cancer treatment is the approval of zolbetuximab (Vyloy) by the FDA in October 2024. Zolbetuximab is a first-in-class drug that targets the claudin 18.2 protein, which is overexpressed in certain gastric and gastroesophageal junction (GEJ) cancers. It is used in combination with fluoropyrimidine- and platinum-based chemotherapy for patients with advanced disease.

Clinical trials have demonstrated the efficacy of zolbetuximab in improving patient outcomes. Patients receiving zolbetuximab experienced a longer progression-free survival (9.2 months compared to 8.2 months in the placebo group) and improved overall survival (16.4 months versus 13.7 months in the placebo group). These results highlight zolbetuximab’s potential to become a cornerstone of treatment for advanced gastric cancer.

Advancements in Immunotherapy

Immunotherapy has revolutionized cancer treatment, including stomach cancer. Pembrolizumab (Keytruda), a monoclonal antibody targeting the PD-1/PD-L1 pathway, enhances the immune system’s ability to detect and destroy cancer cells. The FDA has approved pembrolizumab for patients with recurrent, locally advanced, or metastatic gastric cancer whose tumours express PD-L1 and have progressed after two or more systemic therapies.

Recent guidelines from health authorities like NICE also recommend pembrolizumab as part of first-line treatment for advanced stomach cancers, particularly in patients with PD-L1-positive tumours. Clinical evidence underscores its ability to improve response rates and survival outcomes, positioning it as a critical component of modern gastric cancer therapy.

In addition to pembrolizumab, satricabtagene autoleucel, an investigational therapy targeting CLDN18.2-positive gastric cancers, has shown promise in early clinical trials. These therapies represent the ongoing efforts to harness the immune system and develop targeted treatments for specific gastric cancer subtypes.

Innovations in Surgical Techniques

Surgical advancements have improved both recovery times and treatment outcomes for stomach cancer patients. Minimally invasive laparoscopic and robotic-assisted surgeries are increasingly being adopted for tumour removal. These techniques enable more precise surgeries while minimizing damage to surrounding healthy tissue, reducing complications, and shortening recovery periods.

The integration of precision medicine has further enhanced surgical planning. By analysing a patient’s tumour genetics, healthcare providers can identify specific mutations and tailor treatment plans accordingly. This personalized approach increases the likelihood of successful outcomes and reduces the risk of unnecessary treatments.

Emerging Chemotherapy and Radiation Techniques

Ongoing research is driving the development of new chemotherapy agents aimed at improving efficacy and minimizing side effects. Agents like irinotecan and oxaliplatin are being incorporated into treatment regimens, offering improved outcomes for patients.

One novel approach, heated intraperitoneal chemotherapy (HIPEC), involves delivering heated chemotherapy directly to the tumour site during surgery. This technique has shown promising results, reportedly doubling survival rates compared to traditional methods by enhancing drug delivery to cancerous tissues.

Proton therapy, a highly precise form of radiation treatment, is also being explored for stomach cancer. By targeting tumours with greater accuracy, proton therapy minimizes damage to surrounding healthy tissues, making it particularly beneficial for cancers located near vital organs.

The Road Ahead

These recent advances reflect an evolving understanding of stomach cancer biology and the growing emphasis on personalized treatment strategies. The integration of targeted therapies like zolbetuximab, immunotherapies such as pembrolizumab, and innovative surgical and chemotherapy techniques has significantly improved survival rates and quality of life for patients.

Ongoing clinical trials and research efforts continue to refine these approaches, explore new therapeutic avenues, and expand treatment options for stomach cancer. With continued innovation, the future holds promise for more effective and less invasive treatments for this challenging disease.

References:

Hazard, L., O'Connor, J., & Scaife, C. (2006). Role of radiation therapy in gastric adenocarcinoma.?World journal of gastroenterology,?12(10), 1511–1520. https://doi.org/10.3748/wjg.v12.i10.1511

Joshi, S. S., & Badgwell, B. D. (2021). Current treatment and recent progress in gastric cancer.?CA: a cancer journal for clinicians,?71(3), 264–279. https://doi.org/10.3322/caac.21657

McCloskey, S. A., & Yang, G. Y. (2009). Benefits and challenges of radiation therapy in gastric cancer: techniques for improving outcomes.?Gastrointestinal cancer research : GCR,?3(1), 15–19.

Mihmanli, M., Ilhan, E., Idiz, U. O., Alemdar, A., & Demir, U. (2016). Recent developments and innovations in gastric cancer.?World journal of gastroenterology,?22(17), 4307–4320. https://doi.org/10.3748/wjg.v22.i17.4307

Sexton, R. E., Al Hallak, M. N., Diab, M., & Azmi, A. S. (2020). Gastric cancer: a comprehensive review of current and future treatment strategies.?Cancer metastasis reviews,?39(4), 1179–1203. https://doi.org/10.1007/s10555-020-09925-3

Shitara, K., Shah, M. A., Lordick, F., Van Cutsem, E., Ilson, D. H., Klempner, S. J., ... & Xu, R. H. (2024). Zolbetuximab in gastric or gastroesophageal junction adenocarcinoma.?New England Journal of Medicine,?391(12), 1159-1162. DOI: 10.1056/NEJMc2409512

Ross, R. C., Akinde, Y. M., Schauer, P. R., le Roux, C. W., Brennan, D., Jernigan, A. M., ... & Albaugh, V. L. (2022). The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer.?Frontiers in surgery,?9, 943544. DOI:10.3389/fsurg.2022.943544

National Cancer Institute. Stomach Cancer Treatment. https://www.cancer.gov/types/stomach/treatment

WebMD. New First-in-Class Drug Approved for Advanced Stomach Cancer. https://www.webmd.com/cancer/news/20241024/new-drug-approved-for-advanced-stomach-cancer

Sunrise Oncology Center. What are the new treatments for stomach cancer. https://sunriseoncocare.com/blog/new-best-treatment-for-stomach-cancer-advancements/

CGT Live. Gastric Cancer Awareness Month 2024: Looking Back at Progress for Cell Therapy. https://www.cgtlive.com/view/gastric-cancer-awareness-month-2024-looking-back-progress-cell-therapy