Standardized Individualized Drug Therapy for Advanced Gastric Cancer Chen Xiaobing, Department of Internal Medicine, Henan Provincial Cancer Hospital
Xiaobing Chen, Henan Provincial Cancer Hospital
The treatments for patients with advanced gastric cancer include chemotherapy, targeted therapy, radiotherapy, palliative treatment and so on. How to select first/second/third line treatment scientifically? Firstly, on the macro level, we should adhere to the strategy of “overall concept, whole process management, scientific decision making and humanistic service”; secondly, in the face of each gastric cancer patient, on the micro level, we should “look east and west” (east look: refer to Japan, Korea and other eastern countries; west look: refer to the United States, Europe and other western countries). Secondly, for each patient with gastric cancer, on the microscopic level, we should adhere to the tactics of “following guidelines, referring to experience, combining wishes, and making individual decisions” on the basis of “looking east and looking west” (East: drawing on Eastern countries such as Japan and Korea; West: drawing on Western countries such as the United States and Europe).
First-line chemotherapy
NCCN guidelines: (Modified) DCF, (Modified) ECF, fluorouracil and cisplatin are all Class 1 evidence, two-drug regimens are less toxic and can be given priority, and for patients with high physical status scores, three-drug regimens can be considered.
ESMO guidelines: palliative chemotherapy is recommended with a two- or three-drug regimen of platinum + fluorouracil for Her-2 negative patients and trastuzumab + CF/CX for HER-2 positive patients, in addition to participation in new drug clinical trials.
Overall, two-drug combination regimens are mainstreamed in Asia, considering the balance of efficacy and toxicity, while three-drug combination regimens (ECF/DCF) are mainstreamed in Europe and the United States, emphasizing higher tumor remission rates and efficacy.
In order to facilitate the popularization of standardized treatment for advanced gastric cancer, Prof. Chen Xiaobing has compiled the treatment norms of the Expert Committee on Rational Drug Use of the National Health Planning Commission into the following table for your study.
Clinical breakthroughs are urgently needed in the treatment of two subtypes of gastric cancer, one is diffuse gastric cancer, which is prone to resistance to chemotherapy drugs, and the other is gastric cancer peritoneal metastasis. Here, Prof. Chen Xiaobing also introduced the latest research results in China, using chemotherapy regimen containing tegeo for diffuse gastric cancer and paclitaxel intraperitoneal infusion plus oral tegeo for gastric cancer peritoneal metastasis.
[Second-line chemotherapy].
NCCN guidelines: reference to the drugs already used in the first line and the physical status at that time is needed. Overall, the drugs used are mainly irinotecan and paclitaxel.
After 2010, second-line single-agent chemotherapy for advanced gastric cancer was finally confirmed to be superior to BSC or ASC
In 2013~2014, targeted monotherapy and targeted combination chemotherapy joined the battlefield of second-line treatment
Summary: 1. Second-line chemotherapy regimens reduce the risk of death by 34%
2. Objective response rate (ORR) : 10%
3. Disease control rate (DCR): 40%
4. Different chemotherapy regimens and dosing schedules did not affect the efficacy results
Third-line chemotherapy
There are no norms and standards for third-line chemotherapy drugs.
Apatinib, the first fully self-developed targeted drug in China, has been marketed in China and is currently recommended for third-line treatment. Its efficacy and safety are subject to further clinical validation and observation. Its specific mechanism of action will be introduced in the targeted therapy section below.
Targeted therapy]: At the dawn of time, the first, second and third lines of comprehensive coverage
First-line molecular targeted therapy: Her2 target opens a new era of targeting
her2 is overexpressed in gastric cancer by about 20%. Currently, only Trastuzumab monoclonal antibody has successfully shown significant benefit for gastric cancer treatment, while Lapatinib, another small molecule, has been declared a failure.
The ToGA study, which ushered in a new era of targeted therapy in gastric cancer, showed that Trastuzumab combined with chemotherapy regimens significantly improved treatment outcomes and prolonged survival in patients with high Her2 expression.
Studies are currently underway to determine whether the addition of pertuzumab monoclonal antibody to Trastuzumab will result in better outcomes. To evaluate the efficacy of T-DM1 monotherapy versus paclitaxel-based agents in advanced gastric cancer with Her2 overexpression after recurrence of failure of first-line therapy. We look forward to the final study results.
Second-line molecular targeted therapy: first success with VEGF target
ramucirumab: A new VEGF-targeted monoclonal antibody that acts directly on VEGFR2, the successive “REGARD” (to determine the effectiveness of single-agent ramucirumab) and “RAINBOW” studies ( The results of “REGARD” (which showed that ramolutumab alone was effective) and “RAINBOW” (which showed promising efficacy of ramolutumab in combination with paclitaxel) both showed that 2nd-line treatment for advanced gastric cancer could prolong OS, which is the first VEGF monoclonal antibody that has achieved breakthrough in clinical application in gastric cancer.
Third-line molecular targeted therapy: another success in VEGF target
Apatinib, a small molecule targeted drug targeting VEGF, has been successfully developed in China and clinical studies have confirmed that it has better OS benefit compared to BSC in advanced gastric cancer after failure of 2nd line therapy.
Studies currently underway: promising
-In patients with untreated advanced gastric cancer or tumors with high c-met expression at the gastroesophageal junction, to investigate whether ECX regimens in combination with Rilotumumab monoclonal antibody have a better treatment effect.
To investigate whether mFOLFOX6 in combination with Onartuzumab monoclonal antibody is more effective in patients with advanced gastric cancer or c-met high expression tumor at the gastroesophageal junction.
Prospects of targeted drug therapy for gastric cancer
In patients with advanced gastric cancer who failed 1st-line therapy, the REGARD study showed 2nd-line efficacy of ramucirumab alone and comparable OS survival benefit with docetaxel and irinotecan.
In addition, another pivotal RAINBOW study of ramucirumab was the first phase III trial to demonstrate a significant improvement in OS with 2nd-line therapy in combination with paclitaxel.
-Another popular target is c-Met, with trials of Rilotumumab and Onatuzumab underway.
Other gene-based and immune-related studies are being conducted and published, which will bring more light and progress in the drug treatment of gastric cancer.
Genotyping
Precision medicine led by genetic molecular typing is likely to bring more practical help to clinical individualized treatment, provide specific reference basis for program selection, and lead the breakthrough of gastric cancer individualization. Gene sequencing can help individualize the treatment of tumor patients to achieve better therapeutic effect. The research results released by American Clinical Oncology Annual Meeting showed that more than 80% of doctors changed their original treatment after tumor genetic testing.
[Summary of standardized individualized drug therapy for gastric cancer].
First-line treatment
Two-drug regimen is “highly effective and less toxic” and is the first-line treatment of choice (fluorouracil such as Tegeo + platinum)
Three-drug combination can be considered for those with high PS score (DCF/ECF and its modified version)
For HER2-positive patients, the addition of trastuzumab in combination with chemotherapy is recommended
Second-line therapy
Individualized treatment with reference to first-line drugs already used and PS scores
Benefit from irinotecan-based regimens or paclitaxel-based agents
Post-second-line therapy
Best supportive care is the mainstay, with apatinib showing initial efficacy
Finally, medication is like an army, the details determine success or failure. While scientifically developing a treatment plan, it is also important to pay attention to the toxic reactions and precautions of commonly used chemotherapy drugs.