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Happy New Year! What is the good news in the field of anti-cancer in the past year? I invited 10 good friends who are also top clinical experts in various cancer fields in China to share the anti-cancer progress that deserves the attention of patients in their eyes, I hope it will be helpful to everyone! 2023, let's go together!
List of experts (sorted by last name stroke)
Children's tumor NTRK-targeted drugs and GD2 immunologics
Professor Wang Huanmin
Chief Physician and Director of Department of Oncology, Beijing Children's Hospital, Capital Medical University; Chairman of the Pediatric Oncology Professional Committee of the Chinese Anti-Cancer Association
Childhood tumors are different from adult epithelial cancers in that they are mostly embryonal tumors and mesenchymal-derived sarcomas, with a low burden of gene mutations and more chromosomal structural abnormalities such as amplification, fusion or deletion. Therefore, gene drugs, targeted drugs, etc., which are widely used in the field of adult cancer, rarely show good results in childhood tumors. However, targeted drugs targeting NTRK gene fusion have also shown good results in pediatric tumors, and the objective response rate of lalotinib in childhood solid tumors such as infantile fibrosarcoma has reached 84% and CR rate of 25% in international multi-center clinical trials. Larotinib will be approved for marketing in China in 2022, bringing hope to children with various childhood tumors with NTRK fusion. This outstanding performance of targeted drugs has greatly promoted the development of precision medicine for children's tumors.
Neuroblastoma, known as the "king of childhood cancer", is the most common extracranial solid tumor in childhood, and its main immunological feature is the characteristic antigen-ganglioside GD2 on the surface of tumor cells. Therefore, the research and development of GD2 antibodies has been a hot spot in neuroblastoma research in recent decades. As the first GD2 antibody introduced into China, Kaiserbai was approved for marketing at the end of 2021 and promoted and applied nationwide in 2022, providing immunotherapy opportunities for children with neuroblastoma and further promoting the development of tumor immunotherapy in the field of pediatrics.
Adjuvant/neoadjuvant therapy for pancreatic cancer and immunotherapy for radiotherapy
Professor Tian Yantao
Chief physician of the Department of Pancreatic and Gastric Surgery, Cancer Hospital of Chinese Academy of Medical Sciences; Chairman of the Science Popularization Committee of the Chinese Anti-Cancer Association
In 2022, the final results of a number of comprehensive treatment of pancreatic cancer were announced, which made great contributions to improving the quality of life and prolonging the survival time of pancreatic cancer patients.
The 5-year follow-up results of the PRODIGE24 study, published in the journal JAMA Oncology, randomized eligible patients with pancreatic ductal carcinoma to receive either mFOLFIRINOX adjuvant therapy or traditional standard gemcitabine adjuvant therapy after surgery, and found that mFOLFIRINOX significantly prolonged overall survival compared with gemcitabine treatment, providing strong evidence for the choice of postoperative treatment options for pancreatic cancer.
A multicenter, phase III. clinical trial, PREOPANC, from the Netherlands, evaluated the efficacy of neoadjuvant therapy and direct surgery in patients with resectable and borderline resectable pancreatic cancer, and found that the 5-year overall survival rate was 20.5% in the neoadjuvant chemoradiotherapy group and 6.5% in the direct surgery group, clarifying the value of neoadjuvant therapy in pancreatic cancer.
A randomized controlled and phase II. clinical trial compared the efficacy of stereotactic body radiotherapy + nivolumab and stereotactic body radiotherapy + nivolumab + ipilimumab in patients with metastatic pancreatic cancer, and found that stereotactic body radiotherapy + nivolumab + ipilimumab showed better antitumor activity, and proposed new treatment ideas and treatment options for the treatment of such patients.
Better neoadjuvant therapy for esophageal cancer
Professor Li Yong
Chief Physician, Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, M.D
2022 is a year of further development of neoadjuvant therapy for esophageal cancer, ASCO-GI announced the results of JCOG1109 research in preoperative neoadjuvant chemoradiotherapy, compared with neoadjuvant chemotherapy CF group, neoadjuvant chemotherapy DCF group median overall survival (mOS; not achieving vs.4.6 years) and median progression-free survival (mPFS; not reaching vs.2.7 years) were significantly prolonged, while there was no significant difference in OS and PFS between the neoadjuvant chemotherapy CF group and the neoadjuvant chemotherapy CF combined with radiotherapy group, which gave a new scheme for the choice of neoadjuvant therapy mode for esophageal cancer.
In the phase Ib SCALE-1 study, PD-1 monoclonal antibody combined with short-cycle neoadjuvant chemoradiotherapy (paclitaxel + carboplatin) had a major pathological response (MPR) rate of 80% and a complete pathological response (pCR) rate of 55% in patients with locally advanced resectable esophageal squamous cell carcinoma. The 2022 European Society of Medical Oncology (ESMO) Annual Meeting reported the phase II clinical trial of the new drug sotigalimab (CD40 agonist) combined with chemoradiotherapy (paclitaxel + carboplatin) neoadjuvant therapy for esophageal cancer, with a pCR rate of 36%, including adenocarcinoma pCR rate of 30%, squamous cell carcinoma pCR rate of 60%, and total MPR rate of 64%, which is not inferior or even higher than the pCR rate of combined PD-1 monoclonal antibody in terms of data. It is worth noting that the above neoadjuvant immune combination studies are small samples, and the best combination treatment regimen is expected to be confirmed by large randomized controlled studies.
A new targeted therapy for iodine-refractory differentiated thyroid cancer
Professor Zhu Li
Chief physician and director of the Department of Nail and Breast Surgery, First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Director of Thyroid Cancer Breast Cancer COC
Wang Min
Deputy Chief Physician of the Department of Nail and Breast Surgery, First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Master Supervisor
The incidence of thyroid cancer in mainland China has increased year by year, and the latest data in 2022 shows that the incidence of thyroid cancer in women has risen to the third place among all female tumors. Conventional wisdom holds that thyroid cancer treatment is effective and has low mortality, but this is not entirely the case. The 2022 study showed that as the incidence of thyroid cancer skyrocketed, the number of patients who died from thyroid cancer gradually increased, and the 5-year survival rate of thyroid cancer in China (84.3%) still lagged behind that of developed countries such as the United States (98%).
Differentiated thyroid cancer (DTC) accounts for the vast majority (93%) of thyroid cancers. At present, iodine-refractory DTC is still a difficult point in the treatment of differentiated thyroid cancer. The major advance in the field of thyroid cancer in 2022 is the publication of the results of the COSMIC-311 study. The study included patients with iodine-refractory DTC who had received second-line or above, including lenvatinib or sorafenib, and showed that cabozantinib remained significantly effective in second-line and above. Cabozantinib becomes the first second-line treatment for iodine-refractory DTC and will play an important role in improving the survival of DTC patients. The Department of Breast and Nail Surgery, First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, has been committed to improving the treatment effect of thyroid cancer patients, and has established a comprehensive diagnosis and treatment center for thyroid cancer tumors, relying on a multidisciplinary platform to provide better medical services for thyroid cancer patients.
Future directions of prostate cancer screening
Professor Zhu Yao
Fudan University Cancer Hospital
Chief physician and doctoral supervisor
There are many major studies in the field of prostate cancer in 2022, but the most clinically valuable for me is the GÖTEBORG-2 clinical trial published in the NEJM journal in December. The study addresses the prostate cancer screening dilemma: screening can significantly reduce prostate cancer mortality by detecting early-stage prostate cancer, but screening also found that many indolent prostate cancers lead to unnecessary overdiagnosis and treatment. How to turn the "double-edged sword" of prostate cancer screening into a "far greater than harmful" treatment weapon is a difficult problem that plagues the prostate cancer neighborhood.
The GÖTEBORG-2 study combined PSA screening and multiparametric magnetic resonance sequencing of the prostate to demonstrate that a combination of blood tests and accurate imaging can significantly reduce the detection rate of indolent prostate cancer, while the probability of missing aggressive prostate cancer is also relatively low. After screening for prostate cancer, the research team further subdivided the treatment into two groups, close follow-up monitoring and active local treatment, according to the puncture pathology, to further reduce overtreatment. This study is a well-designed phase III randomized controlled clinical study involving up to 37,887 male participants, and the conclusions are credible.
The results of this study point to the future development direction of prostate cancer screening: blood diagnostic markers represented by PSA are preliminary screening criteria, and then aggressive prostate cancer needs to be diagnosed with the least cost through precise imaging, and gradient treatment plans are made according to the puncture results. Such a diagnosis and treatment scheme can provide the optimal treatment method that matches the biological behavior of prostate cancer, and it is necessary to further optimize the diagnostic specificity of future diagnostic markers, such as the further integration of PSMA imaging and magnetic resonance.
Molecular detection and targeted drugs for ovarian cancer
Professor Liu Jihong
Chief physician of the Department of Gynecology, Sun Yat-sen University Cancer Center and doctoral supervisor; Vice Chairman of the 4th and 5th Committee of the Gynecologic Oncology Branch of the Chinese Medical Association; Chairman-elect of the Gynecologic Oncology Professional Committee of the Chinese Anti-Cancer Association
For a long time, the diagnosis and treatment of ovarian cancer has been a difficult problem in the clinical practice of gynecological tumors. Due to the difficulty of early diagnosis, most patients are diagnosed at an advanced stage, and most patients with advanced ovarian cancer will relapse after treatment, and then relapse, and eventually develop platinum resistance and are refractory. At present, the standard treatment regimen for platinum-resistant ovarian cancer is non-platinum chemotherapy, however, the efficacy rate of chemotherapy in patients with platinum-resistant recurrent ovarian cancer is low and toxic, which is a dilemma and challenge in the field of women's cancer.
In recent years, the development of molecular detection and the development of targeted drugs have brought new hope for the treatment of drug-resistant recurrent ovarian cancer.
The first is the global multicenter SORAYA study, which aims to evaluate the efficacy and safety of a high-expression antibody-conjugate drug MIRV against folate receptor α (FRα) for the treatment of platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer. Ovarian cancer cells have high levels of FRα expression and almost no expression in normal tissues, which provides a new target for ovarian cancer treatment. The study presented updated research data at two international conferences in 2022, and in patients who had previously received 1~2 and 3 line regimens, the efficacy rates of MIRV treatment were 35.3% and 30.2%, and the disease control rates were 58.8% and 45.3%, respectively. Nearly 40% of enrolled patients were stage IV, more than half underwent 3-line systemic therapy, all patients had used bevacizumab, 48% had used PARP inhibitors, and 37% had a platinum-free interval of <3 months after the last platinum-containing chemotherapy. Based on the results of this study, on November 14, 2022, the FDA accelerated the approval of the drug for marketing. Please note that medication prescription information is accompanied by a boxed warning about ocular toxicity, including visual impairment, corneal lesions, dry eye, photophobia, eye pain and uveitis.
Since platinum resistance is multifactorial, combination therapy strategies of multiple targeted drugs have received widespread attention. The ANNE study is a prospective investigator-initiated study to evaluate the efficacy and safety of niraparib in combination with anlotinib (both marketed drugs) in the treatment of platinum-resistant recurrent ovarian cancer.
The study was presented at an international conference in March 2022 and published in full in The Lancet in November. A total of 40 patients with platinum-resistant recurrent ovarian cancer were enrolled, and the inclusion criteria were patients with epithelial ovarian cancer who had received first-line or more platinum-based chemotherapy and were resistant to chemotherapy, of which about 70% had previously received antiangiogenic drugs, the median number of treatment lines was 4 lines, most of the enrolled cases were patients with recurrent ovarian cancer who had undergone multiple therapy, with an effective rate of 50%, median progression-free survival and overall survival of 9.2 months and 15.3 months, respectively, and a 6-month progression-free survival rate of more than 80%. Compared with the two drugs monotherapy, no new drug-related adverse reactions were found in combination therapy, and the most common side effects were hypertension, hand-foot syndrome, and blood adverse reactions, most of which were safe and controllable. The results suggest that niraparib combined with anlotinib, a combination of dual oral and dechemotherapy, can improve tumor response to treatment and improve the quality of life of patients, and may become a new treatment option for patients with platinum-resistant recurrent ovarian cancer. At present, "Anni combination" has been recommended as a treatment recommendation for patients with platinum-resistant recurrent ovarian cancer in the "Guidelines for the Clinical Application of PARP Inhibitors in Ovarian Cancer in China (2022 Edition)"
Novel targeted therapy for gastric cancer targeting Claudin18.2
Professor Xiaotian Zhang
Vice President of Peking University Cancer Hospital, Chief Physician of Department of Digestive Oncology, Doctor of Medicine, Doctoral Supervisor
Claudin18.2 is a transmembrane protein involved in the regulation of tight junctions between cells, and is specifically expressed in about 70% of gastric cancer tumor cells.
In 2022, gastric cancer treatment made a breakthrough in the field of targeting Claudin18.2. Astellas announced that the Phase III SPOTLIGHT clinical trial reached the primary endpoint, and Zolbetuximab is expected to become the world's first Claudin18.2 monoclonal antibody on the market.
The results of CART therapy for Claudin18.2 suggest that the ORR of gastric cancer patients after multi-line therapy failure is as high as 61.1%, which is currently in confirmatory phase II. clinical trials. Clinical trials related to bispecific antibodies and ADC drugs are also advancing rapidly.
The success of targeted Claudin18.2 therapy makes up for the gap of targeted therapy for patients with HER2-negative gastric cancer, greatly expands the applicable population of gastric cancer targeted therapy, and means that the targeted classification of gastric cancer has begun to move from the previous HER2-positive and HER2-negative to the multi-target era.
Antibody conjugates for urothelial/bladder cancer
Professor Shou Jianzhong
Chief physician of the Department of Urology, Cancer Hospital of Chinese Academy of Medical Sciences, doctoral supervisor
Urothelial carcinoma mainly affects the bladder. Patients with metastatic urothelial carcinoma (mUC) have had a low 5-year survival rate in the past, and platinum-based chemotherapy is recommended as the first-line regimen. Clinical treatment options are limited, but the treatment of metastatic urothelial carcinoma has advanced by leaps and bounds with the approval of immunotherapy drugs, antibody conjugate (ADC) drugs, and targeted drugs in mUC indications.
In previous years, immunotherapy related research in the field of urothelial carcinoma has been dominant, and in recent years, ADC drugs have emerged, related research has entered the outbreak stage, and a number of drugs have been approved for the treatment of advanced urothelial cancer, among which the domestic ADC drug (vedicitumab) for HER2 has been approved by the China Food and Drug Administration for the treatment of patients with locally advanced or metastatic urothelial carcinoma (LA/mUC) who have previously received platinum-based chemotherapy, with an ORR of up to 50.5%.
The combination of ADC drugs combined with immunotherapy has shown very exciting treatment results in the field of urothelial cancer research at home and abroad in 2022. The first-line treatment of patients with cisplatin intolerance to LA/mUC with ADC drug (EV) combined with immunization (pembrolizumab) for Nectin-4 had an ORR of 64.5%; The ORR of vedicitumab combined with immunization (teripulimab) in patients with unresectable LA/mUC is as high as 71.8%, of which the ORR is as high as 73.9% as a first-line treatment for advanced urothelial cancer, which is significantly higher than the efficacy rate of platinum-based chemotherapy.
Although ADC drugs or combination immunotherapy are currently mostly studied in cisplatin-intolerant mUC patients, and the number of cases is relatively small, it has clearly demonstrated beneficial efficacy and will strongly challenge the therapeutic status of platinum-containing standard chemotherapy regimens. ADC drugs or combined immunotherapy have also begun to be deployed in neoadjuvant and adjuvant therapy for muscle-invasive bladder cancer, which is expected to become an important research hotspot in the field of urothelial carcinoma anti-tumor in the future.
A new standard of care for HER2-low breast cancer
Professor Luo Ting
Deputy Director of the Breast Disease Center of West China Hospital of Sichuan University
Patients with previously low HER2 expression (IHC2+/FISH- or IHC1+, accounting for about 45%~50% of the total breast cancer patients) with advanced breast cancer were judged HER2-negative because they could not benefit from anti-HER2 therapy. The results of the DESTINY-Breast04 study, published this year, changed this consensus by demonstrating for the first time the breakthrough effect of T-DXd in the treatment of HER2-expressing advanced breast cancer. The results showed that T-DXd resulted in longer PFS (progression-free survival) and OS (overall survival) than chemotherapy in CDK4/6 inhibitor-treated populations, and a consistent trend of better benefit of T-DXd was seen in all subgroups.
The DESTINY-Breast04 study results changed the treatment landscape of HER2-low expression advanced breast cancer and established a new standard of treatment, making T-DXd the first anti-HER2 drug to significantly improve PFS and OS statistically and clinically compared with chemotherapy, and also redefined this group of people who were previously classified as HER2 negative as HER2 low expression people. Based on this, the NCCN and ASCO guidelines were rapidly updated and the FDA accelerated approval of T-DXd for the treatment of HER2-low mBC.
Oncolytic viral therapy for gliomas
Professor Qin Zhiyong
Chief physician of neurosurgery at Huashan Hospital affiliated to Fudan University; Vice Chairman of the Glioma Special Committee of the Chinese Medical Doctor Association; Chairman-elect of the Neuro-Oncology Committee of the Chinese Society of Clinical Oncology
Glioblastoma (GBM) accounts for about 35-40% of malignant brain tumors, and the median survival after comprehensive treatment such as surgery, radiotherapy and chemotherapy is about 16 months, and the 5-year survival rate is less than 10%.
The clinical progress most likely to affect the treatment of GBM in 2022 is the phase II clinical trial of oncolytic virus G47Δ for the treatment of relapsed glioblastoma published by Nature Medicine in August 2022. This is the first oncolytic virus conditionally approved for the treatment of malignant glioma, which targets infected tumor cells by genetically modifying a virus with replication viability, and kills tumors by the dual mechanism of direct proliferation and lysis and indirect induction of anti-tumor immunity.
The median OS of 19 treated participants reached 20.2 months, and 5 survived for more than 3 years. The excellent clinical trial results of this oncolytic virus are another big step towards achieving the goal of long-term survival of GBM patients.
Thank you to all the experts for their interpretation, and thank you to all scientists and medical workers for their unremitting efforts, which brought so many gratifying progress! In the next article, we will take stock of the breakthroughs in more popular fields such as lung cancer, and look forward to it.
I believe that there will be more and more good news in the future, 2023, let's cheer together~
Happy New Year to all! Salute to life!
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