CSCO Pancreatic Cancer Guidelines Medical Treatment Update Highlights 2022 CSCO Guidelines Meeting

*Only for medical professionals to read and refer to the update points of pancreatic cancer medical treatment to clarify! According to the forecast data of the World Health Organization (WHO) in 2020, the number of pancreatic cancer cases worldwide is 495,700, of which 125,000 are in China, accounting for about a quarter of the global total
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In addition, the treatment of pancreatic cancer is difficult, the 5-year survival rate is less than 10%, and 80%-85% of pancreatic cancer patients are inoperable or metastatic pancreatic cancer
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Since the last update of the CSCO Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in 2020, the new version of the "2022 CSCO Guidelines for the Diagnosis and Treatment of Pancreatic Cancer" (referred to as the "Guidelines") was finally released after two years
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At this guideline meeting, Professor Cui Jiujie of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine shared the medical treatment part of the guideline
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"This update mainly includes the important clinical research on pancreatic cancer published in the six major conferences of ASCO in 2020 and 2021, ESMO in 2020 and 2021, ASCO GI in 2021 and 2022, and PubMed from 2020 to the present
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The
Medical Community Tumor Channel" is organized as follows, for readers
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Advances in perioperative drug therapy 1.
SWOG S1505: mFOLFIRINOX vs gemcitabine/nab-paclitaxel (Gem/nabP) perioperative treatment of resectable pancreatic ductal adenocarcinoma (PDA) study results (randomized phase II clinical study), the primary endpoint is 2-Year Overall Survival (OS) Rate (2020 ASCO): Patients with newly diagnosed resectable pancreatic cancer received mFOLFIRINOX or gemcitabine/nab-paclitaxel 12 weeks before and 12 weeks after surgery; The 2-year OS rates in the protein paclitaxel group were 43.
1% (22.
4 months) and 46.
9% (23.
6 months), respectively; Conclusions: The perioperative mFOLFIRINOX and gemcitabine/nab paclitaxel regimens have similar efficacy, safety and surgical resection rates.
similar
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2.
ESPAC-5F study: immediate surgery versus preoperative gemcitabine combined with capecitabine or FOLFIRINOX or concurrent chemoradiotherapy for neoadjuvant treatment of borderline resectable pancreatic cancer, a four-arm, prospective international multicenter randomized phase II study (2021 ESMO): Patients with resectable pancreatic ductal adenocarcinoma were randomized to gemcitabine + capecitabine + surgery (n = 20) or FOLFIRINOX + surgery (n = 20) or concurrent chemoradiotherapy + surgery (n = 16) or immediate surgery (n = 32)
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The primary endpoint of the study was the surgical resection rate; the results showed that the resection rate of immediate surgery was not significantly different from the resection rate after neoadjuvant therapy (62% vs 55%) (P=0.
668); The annual survival rate was higher (77% vs 42%, P<0.
001); patients with FOLFIRINOX regimen had the highest one-year survival rate (84% vs 79% vs 64%); FOLFIRINOX regimen had a higher incidence of toxicity, but overall The number of participants in each group in this study is relatively small, but for patients with borderline resectable pancreatic cancer, neoadjuvant therapy should be considered
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3.
APACT study (postoperative adjuvant therapy) 5-year survival data update (2021 ESMO): APACT study is a comparison of nab-paclitaxel (Nab-P) combined with gemcitabine (Gem) and Gem monotherapy for postoperative adjuvant therapy of pancreas Multicenter, international, open-label, randomized phase III study of efficacy and safety in cancer; results showed no significant difference in the primary endpoint (DFS assessed by an independent review committee) between the two groups (19.
4 months vs 18.
8 months; HR 0.
88; P=0.
1824); but Nab-P+Gem improved 5-year OS in pancreatic cancer patients compared with Gem monotherapy
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The median OS of the two groups was 41.
8 months and 37.
7 months, respectively; HR 0.
80; P=0.
0091, and the 5-year OS rates were 38% and 31%, respectively
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4.
Update of Unicancer PRODIGE 24/CCTG PA6 study data: comparing the safety and efficacy of mFOLFIRINOX and gemcitabine in adjuvant treatment of pancreatic cancer.
Effective adjuvant treatment regimen; univariate analysis showed that the 5-year OS rates of patients who completed all cycles of treatment and those who did not complete the treatment were 41.
9% and 27.
4%, respectively (P=0.
002), and this difference also existed in the two treatment groups; This study is currently the longest-surviving adjuvant therapy study for pancreatic cancer
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Advances in advanced drug therapy 1.
Phase I/II study of efficacy and safety of Zenocutuzumab in NRG1-fused advanced pancreatic cancer and other solid tumors (2021ASCO) Neuregulin 1 (NRG1), a ligand that binds to HER3, promotes Activation of HER2/HER3 heterodimers and PI3K/AKT/mTOR signaling; patients with locally advanced, unresectable, or metastatic solid tumors harboring NRG1 gene fusions were enrolled and treated with Zenocutuzumab until disease progression
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The primary endpoint of the study was objective response rate (ORR); the results showed that 12 patients with pancreatic cancer had an ORR of 42% and a disease control rate (DcR) of 92%
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This is a very good result for advanced pancreatic cancer after failure of standard therapy; more patients with objective responses occurred two months after treatment, and patients with ORR had a longer time to DoR
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2.
Results of a randomized phase II study of gemcitabine + nab-paclitaxel vs gemcitabine + nab-paclitaxel + durvalumab (D) + Tremelimumab (T) in the first-line treatment of metastatic pancreatic ductal adenocarcinoma (2020 ESMO): patients enrolled in the study There are many patients, with a sample size of 180 cases; the results showed that the primary endpoint OS of the two groups was 9.
8 months and 8.
8 months, respectively, and quadruple therapy failed to significantly improve OS and PFS; %) and ORR (44.
2% vs 32.
9%), but did not reach statistical significance
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Subsequently, a correlation analysis at 2021 ASCO explored the association of germline ATM gene mutation status with the benefit of immunotherapy: the results showed that patients with germline ATM gene mutations (9.
2%, 16 of 174 patients) received a The on-treatment benefit was greater than with chemotherapy (13.
9 months vs 4.
9 months); this suggests that patients with ATM mutations or problems with DDR signaling may benefit more from immunotherapy
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3.
CISPD3 study: a single-center, randomized, open-label phase III trial of sintilimab combined with mFOLFIRINOX versus mFOLFIRINOX alone in Chinese patients with metastatic and recurrent pancreatic cancer (2022 ASCO GI): 110 eligible patients Patients were randomly assigned (1:1) to sintilimab (200 mg every 3 weeks) + mFOLFIRINOX (irinotecan 85 mg/m2, oxaliplatin 68 mg/m2, then 5-FU 2400 mg/m2 every 2 weeks ) or mFOLFIRINOX group
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The primary endpoint was OS, and secondary endpoints included PFS, ORR, DCR, and safety; median OS was similar between the sintilimab plus mFOLFIRINOX and mFOLFIRINOX groups (10.
9 months vs 10.
8 months; HR 1.
083; 95% CI 0.
6843 -1.
690)
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Median PFS was 5.
9 months in the sintilimab plus mFOLFIRINOX group and 5.
73 months in the mFOLFIRINOX group (HR 0.
9324; 95% CI 0.
6158-1.
412); the ORR was 50% in the sintilimab plus mFOLFIRINOX group compared with 50% in the mFOLFIRINOX group.
was 23.
9% (P=0.
010); how to convert ORR benefit into PFS and OS benefit is the key to future research
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4.
Activity and Safety Results Update for Adagrasib (MRTX849) in Patients with Unresectable or Metastatic Pancreatic Cancer (PDAC) and Other Gastrointestinal (GI) Tumors Carrying a KRAS G12C Mutation (2022 ASCO GI): KRAS is an Most frequently mutated oncogene, occurring in approximately 90% of pancreatic cancers, of which approximately 2% are KRAS G12C mutated; Adgrasib (MRTX849) is a highly selective KRAS G12C inhibitor that selectively binds KRAS G12C irreversibly , locking it in an inactive state; KRYSTAL-1 (NCT03785249) is a multi-cohort phase I/II study to evaluate the efficacy of adagrasib monotherapy or combination therapy in patients with advanced solid tumors with KRAS G12C mutation, which contains 12 patients with pancreatic cancer (median number of lines of therapy, 3; median follow-up, 8.
1 months), 10 of whom were evaluable for clinical activity; ORR achieved in 10 patients with KRASG12C-mutated pancreatic ductal adenocarcinoma 50%, including 1 unconfirmed partial response (PR), with a DcR of 100%
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The median duration of response (mDoR) was 7.
0 months, the median follow-up was 8.
1 months, and the median PFS was 6.
6 months (95% CI 1.
0-9.
7 months)
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Finally, Prof.
Cui Jiujie concluded: From 2020 till now, the field of pancreatic cancer has high evidence-based medical evidence, and clinical studies with positive results are relatively lacking; the exploration of perioperative neoadjuvant therapy is a hot topic, and neoadjuvant therapy has been widely used at present.
Approved, but there is currently a lack of high-level evidence for the choice of regimens.
FOLFIRINOX and AG regimens are the preferred regimens; in the basket clinical study of advanced pancreatic cancer, some pancreatic cancer patients may have specific targets, which can significantly prolong patient survival; The current results of immunocombination chemotherapy are improving the objective response and disease control rate, but the prolongation of overall survival is limited
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Novel biomarkers need to be explored to find potential benefit populations of immunotherapy
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Expert Profile Professor Cui Jiujie, MD, PhD, Department of Oncology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 2012-2014 Visiting MD Anderson Cancer Center in the United States, chaired the National Natural Science Foundation of China Youth Fund, and won the Shanghai "Medical Garden Rising Star" Young Medical Talents Training Program , Shanghai Jiaotong University School of Medicine "Kowloon Medical Outstanding Young Talent Award" published more than 30 SCI papers, with a total impact factor of more than 150 points Member and Secretary of the Pancreatic Cancer Expert Committee Member of the CSCO Tumor Nutrition Therapy Expert Committee Member of the CSCO Liver Cancer Expert Committee Member of the Shanghai Anti-Cancer Association Pancreatic Cancer Expert Committee Member