Editorial Note: From September 25 to 29, 2024, the highly anticipated 27th Chinese Clinical Oncology Annual Conference and CSCO Annual Meeting took place in Xiamen. Dr. Rongbo Lin of Fujian Cancer Hospital shared key findings from his team’s research in gastric cancer. During the conference, Oncology Frontier conducted an in-depth interview with Professor Lin, discussing the clinical applications of the POFI and POF regimens for advanced gastric cancer.

Oncology Frontier: Could you provide an overview of the preliminary findings from the POFI regimen combining tislelizumab with POFI for first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma? How does this regimen compare to traditional treatments, and what are its advantages? Do you foresee this regimen becoming the new standard for gastric cancer treatment?

Dr. Rongbo Lin: I’m delighted to introduce the concept behind the POFI regimen. We developed it by adding irinotecan to the POF regimen (paclitaxel, oxaliplatin, and 5-FU). The POF regimen, which is quite similar to the FLOT regimen used internationally, has been widely adopted in China due to its safety and efficacy. Building on this foundation, we incorporated irinotecan, adjusting the doses of paclitaxel and irinotecan accordingly, and re-evaluated safety. We further combined POFI with BeiGene’s tislelizumab, aiming to increase the production of new tumor antigens and assess if immunotherapy could enhance patient outcomes. This approach has demonstrated impressive efficacy, with a 100% response rate and a median progression-free survival (PFS) of approximately 11 months.

Interestingly, we found no significant difference in efficacy between PD-L1 positive and negative patients. Given recent FDA recommendations against immunotherapy in CPS<1 patients, we are exploring whether increased chemotherapy intensity could improve efficacy for patients with CPS<5. This remains a key focus of our ongoing research.

Oncology Frontier: As one of the principal authors of the CSCO gastric cancer treatment guidelines, how did you approach integrating the POF regimen? What impact has it had in clinical settings? How should community physicians best understand and apply the POF regimen to improve gastric cancer treatment outcomes?

Dr. Rongbo Lin: In my early clinical practice, I started with the FLOFOX regimen, and my mentors also began combining paclitaxel and 5-FU at a relatively low dose. While safe, it did not deliver ideal outcomes in terms of tumor response duration, PFS, and overall survival (OS). Inspired by breast cancer treatments, particularly biweekly paclitaxel regimens, I tested a 135 mg/m2 dose of paclitaxel combined with 5-FU. We then incorporated oxaliplatin, achieving positive tolerability and efficacy, which led to a Phase II trial to further validate the results.

When designing the POF regimen, we noted the DCF regimen (docetaxel, cisplatin, and 5-FU) in international studies, but its significant toxicity limited its use. Our research confirmed the superiority of the three-drug POF regimen over two-drug combinations, and in 2019, we reported the results at ASCO GI, showing a balance of efficacy and manageable toxicity. Based on these findings, the CSCO expert panel approved including POF in the gastric cancer treatment guidelines.

Compared to FLOT, which is supported by the GASTFOX study, POF has advantages. FLOT uses docetaxel, known for higher hematologic toxicity than paclitaxel, which patients tolerate better. Some specialists use albumin-bound paclitaxel, yet studies only confirm non-inferiority in gastric cancer’s second-line settings, with higher hematologic and neurotoxic effects. Thus, in clinical practice, we stick with standard paclitaxel in the POF regimen, achieving robust efficacy and low toxicity.

The POF regimen holds particular value for community physicians. In smaller hospitals, where many patients are already familiar with treatments involving oxaliplatin, paclitaxel, and fluorouracil, POF can be effective even for patients who previously showed resistance to individual drugs. This regimen can help community doctors manage patients referred back from higher-level hospitals, supporting treatment efficacy at the local level.

With three drugs, managing toxicity is crucial. In our practice, we developed a concept called “fast recovery from chemotherapy,” maintaining close communication with patients through phone and WeChat to promptly address issues and manage toxicity early on. Additionally, encouraging regular exercise helps reduce treatment-related toxicity, minimizing adverse events without extensive use of growth factors.

Another key approach is prompt intervention when severe side effects occur, such as using anti-inflammatory drugs to manage oral mucositis or neutropenia. For any colleagues encountering similar issues with POF, I’m always available to offer support.

Dr. Rongbo Lin Chief Physician of Medical Oncology, Fujian Cancer Hospital Vice Chair, Comprehensive Evaluation of Oncology Committee, China Anti-Cancer Association Chair, Cancer Pain Committee, Fujian Anti-Cancer Association Member, CSCO Gastric Cancer Expert Committee and Lead Author of CSCO Gastric Cancer Guidelines