Pancreatic cancer is a very malignant gastrointestinal tumor, and its incidence has shown an increasing trend year by year in recent years, and the clinical manifestations are characterized by insidious disease, rapid development and poor prognosis. As the "king of cancers", the survival rate of pancreatic cancer is not satisfactory, about 80% of patients are in advanced stages at the time of diagnosis, and the median survival period is less than 1 year
1
。 At present, gemcitabine-based chemotherapy regimens and radiotherapy methods are not effective in treating patients, and there is an urgent need to develop effective and safe therapeutic drugs.
In the curtain that has just come to an end
The NOTABLE study stood out at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and was named a "Breakthrough" and "Excellent Paper." To this, the doctor
Professor Hao Chunyi of Peking University Cancer Hospital was invited to introduce the new progress of interpreting new auxiliary research and the clinical value of NOTABLE research.
Expert Profiles
Professor Hao Chunyi
- Director of the International Cooperation Department of Peking University Cancer Hospital, Executive Deputy Director of The Department of Major Surgery
- Director of the Center for Soft Tissue and Retroperitoneal Tumors at Peking University Cancer Hospital, director of the Hepatobiliary and Pancreatic Extramural Ward II
- Professor Emeritus, Cardiff University, UK
- Chairman of the "CSCO Pancreatic Cancer Expert Committee" of the Chinese Society of Clinical Oncology
- Chairman of the Soft Tissue Oncology Expert Committee of the Chinese Medical Promotion Association
- Vice Chairman of the "CSCO Gastrointestinal Neuroendocrine Tumor Expert Committee" of the Chinese Society of Clinical Oncology
- Secretary General of the Liver Cancer Expert Committee of the Chinese Medical Promotion Association
- Member of the Pancreatics Group of the Surgery Branch of the Chinese Medical Association
- Standing Director of Chinese Society of Clinical Oncology
- Standing Director of China International Medical Exchange and Promotion Association
- Leading talents of Beijing High-level Innovation and Entrepreneurship Talent Support Program
- Experts who enjoy special allowances from the State Council
The "king of cancer" adjuvant chemotherapy is a powerful weapon to prolong the survival of pancreatic cancer patients
Professor Hao Chunyi introduced that pancreatic cancer is a malignant tumor with a rapid increase in incidence in mainland China, and the degree of malignancy and fatality rate are extremely high, but the development of treatment methods is very slow, and the overall 5-year survival rate of pancreatic cancer is only 9%2. Surgery is still the main means of pancreatic cancer that may be cured, but more than 80% of patients in the clinic lose the opportunity to operate, even if the 5-year survival rate of patients undergoing surgical resection is very low, for the treatment of pancreatic cancer, surgery alone can not meet the treatment needs of patients. Therefore, perioperative treatment of adjuvant therapy, neo-assisted and adjuvant neo-assisted combination has become a hot topic in pancreatic cancer treatment, and we hope to extend the disease-free survival and overall survival of pancreatic cancer patients through such treatment. According to guidelines, patients with pancreatic cancer should receive various types of treatment after surgery, particularly adjuvant therapy with evidence-based medical evidence.
Professor Hao said that for patients with resectable or critically resectable pancreatic cancer, the neoadjuvant treatment regimen mostly uses gemcitabine combined albumin-binding paclitaxel, and in some areas, the albumin pegisool combined with the tigiosquiox protocol is used, while the FOLFIRINOX / mFOLFIRINOX regimen (5-FU + calcium folinate + irinotecan + oxaliplatin) is less used in China than in Western countries. Postoperative adjuvant therapy regimens recommend gemcitabine or fluorouracil-based therapy, and combination chemotherapy regimens are recommended for patients with good physical fitness, including gemcitabine plus capecitabine, mFOLFIRINOX, etc.; For patients with poor physical fitness, gemcitabine or fluorouracil monotherapy3 is recommended, with adjuvant chemotherapy starting as soon as possible within three months postoperatively and lasting as little as 6 months. In addition, Professor Hao said that the efficacy of postoperative auxiliary radiotherapy is still controversial, the lack of high-level evidence-based medical evidence, there is no consensus at present, it is recommended that everyone actively participate in and organize relevant clinical research, so as to better meet clinical needs.
New adjuvant treatment, a new weapon to fight against the "king of cancer"
Professor Hao introduced that in the field of neoadjuvant therapy for pancreatic cancer at this year's ASCO conference, the NEONAX trial and NCDB research deserve everyone's attention. Among them, the NEONAX trial-gemcitabine combined with albumin paclitaxel plays a role in the perioperative or adjuvant treatment of resectable pancreatic cancer. The study included 127 patients with resectable pancreatic cancer in German clinical centers, who were randomly assigned to perioperative periods (2 preoperative cycles and 4 postoperative cycles, group A) or adjuvant therapy (6 cycles, group B), who received gemcitabine/albumin paclitaxel, respectively. The findings showed that gemcitabine/albumin paclitaxel showed good tolerance in perioperative treatment in the intended therapy (ITT) population with a median OS of 25.2 months4. In addition, Professor Hao also shared an NCDB study that neoadjuvant chemotherapy can improve the prognosis of patients undergoing surgery in stage I.A or I.B. The study included 6613 patients with pancreatic cancer who underwent surgery in stage IA or IB, 1533 patients who received neoadjuvant or perioperative chemotherapy in the neoadjuvant treatment group, and 5080 patients who received postoperative chemotherapy in the adjuvant treatment group. The results of the study showed that neoadjuvant therapy increased the R0 resection rate and improved patient OS5 compared with the adjuvant treatment group.
Figure 1 NEONAX study
Figure 2 NCDB study
The NOTABLE study is expected to change the treatment pattern of advanced pancreatic cancer
The "Registered Clinical Study of Nitalizumab combined with gemcitabine in the treatment of locally advanced or metastatic pancreatic cancer of KRAS wild type (NOTABLE study)" co-led by Chinese scholars Professor Qin Shukui and Professor Li Jin was released. Professor Hao Chunyi said that the NOTABLE study is not only a major breakthrough in the field of pancreatic cancer treatment, but also represents the global attention and recognition of Chinese scholars- led clinical research. The main endpoint results of the study were reported at this conference, and the results showed that the mOS of the experimental group was significantly longer than that of the control group (FAS population: 10.9 months vs 8.5 months, HR=0.50, p=0.024; PPS population: 11.5 months vs 8.5 months, HR=0.60, p=0.039) in both the full-analysis set (FAS) and the protocol-compliant analysis set (PPS) population.6 In the FAS population, the median progression-free survival (mPFS) in the trial group was significantly prolonged (4.2 months vs 3.6 months, HR=0.56, p=0.013). Thus, nituzumab combined with gemcitabine can significantly reduce the risk of death and disease progression in patients, and the benefits are more significant for patients who have not been treated surgically.
Figure 1 NOTABLE study design
Figure 2 Total survival (full analysis set)
Professor Hao Chunyi believes that pancreatic cancer is one of the most deadly malignant tumors, most patients are in advanced stages when they are diagnosed, and the median OS is only 6 to 8 months. In recent years, a variety of new treatment options have made progress, but the treatment of pancreatic cancer has not achieved significant breakthroughs, and more efficient treatment drugs and programs are urgently needed. THE NOTABLE study focuses on the ingenious research design of KRAS wild-type patients, and an important breakthrough in the treatment of advanced pancreatic cancer has opened a new era of targeted therapy based on molecular biomarker enrichment populations, which has important scientific significance and clinical value, and is expected to change the treatment pattern of advanced pancreatic cancer.
Multi-party exploration to help pancreatic cancer patients regain their lives
With the transformation of pancreatic cancer treatment mode from the past "surgery first" to multidisciplinary comprehensive treatment, perioperative comprehensive treatment has also attracted more and more attention. Professor Hao pointed out that in recent years, the chemotherapy drugs represented by gemcitabine have been recommended by major guidelines for neoadjuvant or adjuvant therapy for pancreatic cancer, although researchers have made a lot of efforts in the dosage form of chemotherapy drugs and the development of new drugs, but there are still many controversies about the targeted therapy and immunotherapy of neoadjuvant therapy. Pancreatic cancer is a cold tumor, with primary drug resistance, it is difficult to fundamentally improve the prognosis of pancreatic cancer by the development of surgical technology alone, and it is also necessary to develop new chemotherapy, targeted and immunotherapy drugs to improve the treatment effect of pancreatic cancer, NOTABLE research has brought a new dawn to the treatment of pancreatic cancer.
Professor Hao also shared a 2020 clinical study published in JCO's PREOPANC Phase III. on concurrent chemoradiotherapy based on fluorouracil or gemcitabine, although the primary study endpoint OS (16.0 months vs. There was no significant benefit at 14.3 months, P=0.096), but the R0 resection rate (71% vs. 40%, P<0.001) was beneficial, and patients who underwent surgical resection into adjuvant therapy had OS at 35.2 months vs. 19.8 months (P=0.029)3.
Professor Hao believes that nituzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that can disrupt the interaction between EGFR and its ligands, specifically block the EGFR signaling pathway, mediate antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and other immune effects, induce EGFR endocytosis and degradation, NOTABLE reported at this ASCO conference The study shows us the significant benefits of nitalizumab plus gemcitabine for advanced pancreatic cancer, which makes us expect that nittozumab may bring higher benefits to patients if used for neoadjuvant therapy for pancreatic cancer. At present, the use of nitalizumab for other tumor species in the perioperative period is being explored, and we expect that nitalizumab can bring a new change in the treatment pattern of new adjuvant and adjuvant therapy for pancreatic cancer.
Bibliography:
1.ZHU Xinzhe, LI Hao, XU Huaxiang, et al. New progress in pancreatic cancer research and diagnosis and treatment in 2021[J]. China Oncology Journal 2022 Vol. 32, Issue 1, pp. 1-12, ISTIC PKU CSCD CA, 2022.
2.Huang Huiying, Cao Baoshan. Perioperative treatment and full-course management of resectable pancreatic cancer[J]. Chinese Clinical Oncology, 2021, 48(2): 85-92.
3. Guideline Working Committee of Chinese Society of Clinical Oncology, Guidelines for diagnosis and treatment of pancreatic cancer 2020.People's Medical Publishing House.
4.Thomas Jens Ettrich, Waldemar Uhl, Marko Kornmann, et al. Perioperative or adjuvant nab-paclitaxel plus gemcitabine for resectable pancreatic cancer: Updated final results of the randomized phase II AIO-NEONAX trial.2022 ASCO. abstr 4133.
5.Noah Rozich, Maharaj Singh, Isaac Kriley, et al. Neoadjuvant chemotherapy is associated with improved outcomes in patients with stage 1A and 1B pancreatic cancer undergoing surgery: An NCDB study.2022 ASCO. abstr 4157.
6.Shukui Qin, et al. Nimotuzumab combined with gemcitabine versus gemcitabine in K-RAS wild-type locally advanced or metastatic pancreatic cancer: A prospective, randomized-controlled, double-blinded, multicenter, and phase III clinical trial.2022 ASCO. abstr LBA4011.
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