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As of early this morning, during the 2021 American Society of Clinical Oncology (ASCO) annual meeting, the New England Journal of Medicine (NEJM) and The Lancet have simultaneously published 6 major clinical trial results.
It is also said that JAMA and BMJ of the four major medical journals have not yet published papers
.
Among them, Lancet today announced the results of a phase 3 randomized controlled clinical trial led by Professor Ma Jun from the Cancer Center Affiliated to Sun Yat-sen University and participated by 14 hospitals in China
.
This trial studied the efficacy and safety of capecitabine rhythm adjuvant chemotherapy for patients with locally advanced nasopharyngeal carcinoma who received radical concurrent radiotherapy and chemotherapy
.
The results showed that receiving capecitabine rhythm chemotherapy for this type of nasopharyngeal cancer patients can significantly improve the 3-year tumor-free survival rate and overall survival rate, and the safety is better
.
The total cost of capecitabine maintenance treatment for one year is less than 5,000 yuan, and it is oral treatment, which is convenient to use and has a high degree of patient acceptance.
It is conducive to promotion to the grassroots.
Its cost performance and popularity are self-evident
.
During the 2019 ASCO annual meeting, NEJM published another nasopharyngeal cancer clinical trial by Ma Jun's team, namely the use of gemcitabine combined with cisplatin (GP) induction chemotherapy before concurrent radiotherapy and chemotherapy
.
We have invited Dr.
Zhang Yuan, the first author of the paper, and Prof.
Jun Ma, the last author, to introduce the research and publication experience (see "It is less than 1 month from submission to NEJM acceptance.
Teachers and students will tell you how this is done.
" ")
.
The editorial department of "NEJM Frontiers in Medicine" compiled the main points of these 6 papers for readers
.
Capecitabine beat adjuvant treatment of locally advanced nasopharyngeal carcinoma has a significant effect.
Looking for clues in failure.
For locally advanced nasopharyngeal carcinoma, especially the subgroup of patients with poor prognostic factors, concurrent radiotherapy and chemotherapy is the main method to cure the disease
.
However, in patients with complete clinical remission, about 30% of patients will have local recurrence or distant metastasis
.
Therefore, finding an effective and safe adjuvant treatment plan is extremely important for these patients
.
Previous studies have selected the classic cisplatin and fluorouracil regimen or the emerging gemcitabine combined with cisplatin regimen as adjuvant chemotherapy drugs
.
However, the results of both studies showed that these adjuvant chemotherapy regimens failed to improve patient survival
.
Ma Jun and others analyzed the shortcomings of previous studies.
They believe that due to the toxicity of previous adjuvant chemotherapy, patients who have received radical radiotherapy and chemotherapy are difficult to tolerate, resulting in a completion rate of only 40% to 60% of adjuvant chemotherapy.
This may be due to the previous adjuvant chemotherapy.
Reasons why chemotherapy is ineffective
.
Capecitabine is a classic chemotherapeutic drug that has been used clinically for many years.
Unlike traditional chemotherapy that uses the maximum tolerated dose to treat tumors, capecitabine can be administered for a long time by low-dose, long-term oral administration of "beating" Maintained at a relatively low blood drug concentration, which can reduce toxic side effects while continuing to fight tumors, and is especially suitable for maintenance treatment of patients after radiotherapy and chemotherapy
.
Inspired by this, Sun Yat-sen University took the lead in launching a Phase 3 clinical trial of capecitabine rhythm chemotherapy for adjuvant treatment of locally advanced nasopharyngeal carcinoma
.
Significant curative effect and outstanding advantages.
This is a multi-center, open-label, parallel group, randomized controlled trial.
A total of 406 patients with locally advanced nasopharyngeal carcinoma were enrolled.
The patients were randomly assigned to the adjuvant treatment group (capecitabine beats).
Chemotherapy group) and clinical observation group (standard treatment group)
.
Patients in the standard treatment group did not receive adjuvant treatment, only routine review
.
Patients in the capecitabine rhythm chemotherapy group received low-dose capecitabine (650 mg/m2, twice a day) for one year
.
The primary endpoint of the trial is the 3-year failure-free survival (FFS), which is the time from randomization to tumor recurrence, metastasis, or death from any cause
.
Secondary endpoints include overall survival, survival without distant metastasis, survival without local recurrence, safety, and quality of life
.
The test results showed that after a median follow-up of 38 months, there were 29 recurrences or deaths in the capecitabine rhythm chemotherapy group (14%) and 53 cases (53%) in the standard treatment group
.
In the intention-to-treat group, the cumulative incidence of disease recurrence or death in the capecitabine rhythm chemotherapy group was 16.
6%, while that in the standard treatment group was 29.
0%
.
The 3-year tumor-free survival rate of the capecitabine-beat chemotherapy group was 85.
3% (95% CI, 80.
4%~90.
6%), while the standard treatment group was 75.
7% (95% CI, 69.
9~81.
9); disease recurrence or The hazard ratio for death was 0.
5 (95% CI, 0.
32 to 0.
79)
.
The 3-year overall survival rate of the capecitabine chemotherapy group (93.
3%; 95% CI, 89.
7%-97.
1%) was also significantly higher than that of the standard treatment group (88.
6%; 95% CI, 84.
2%-93.
2%), and the risk of death The ratio was 0.
44 (95% CI, 0.
22 to 0.
88)
.
At the same time, the 3-year survival rate without distant metastasis and survival rate without local recurrence in the capecitabine beat chemotherapy group were higher than those in the standard treatment group
.
The author also conducted a subgroup analysis based on tumor stage, lymph node stage, and disease stage
.
The results showed that the tumor-free survival rate of the capecitabine rhythm chemotherapy group was higher than that of the standard treatment group in each subgroup
.
The author also specifically pointed out that regardless of whether the patient has received induction chemotherapy, the efficacy of the capecitabine rhythm chemotherapy group is better than that of the standard treatment group
.
Controllable safety In terms of safety, the incidence of grade 1 or grade 2 adverse events in the capecitabine rhythm chemotherapy group was 73%, and that in the standard treatment group was 51%
.
The incidence of grade 3 adverse events in the two groups was 17% and 6%, respectively
.
The most common adverse event in the capecitabine rhythm chemotherapy group was hand-foot syndrome (58%), of which 18% were grade 3 adverse events
.
The adverse events of the blood system include anemia (35%) and leukopenia (27%)
.
Other common adverse events include fatigue (27%) and nausea (22%)
.
However, most of the adverse events in the capecitabine rhythm chemotherapy group were grade 1 or 2, and with the exception of hand-foot syndrome, the incidence of grade 3 or 4 adverse events was similar in the two groups
.
No serious adverse events were reported in either group
.
The authors also used the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to compare the quality of life of the two trial participants
.
The results found that the scores of the two groups at baseline were similar; and during the treatment period, the range of changes in the scores from the baseline had no clinical significance
.
This shows that capecitabine beat chemotherapy did not significantly affect the quality of life of patients
.
Precisely because of its good safety, although some patients suspended treatment or reduced their dose due to adverse events, 74% of patients in the rhythm chemotherapy group completed the one-year planned treatment, and the relative dose intensity of capecitabine reached 98.
1%
.
It is expected to rewrite the guidelines.
The significance of this study is that the authors confirmed for the first time in a phase 3 randomized controlled trial that capecitabine rhythm chemotherapy adjuvant treatment of high-risk locally advanced nasopharyngeal carcinoma can improve the survival rate of patients
.
The NCCN guidelines used concurrent chemoradiation combined with adjuvant chemotherapy as the standard treatment for locally advanced nasopharyngeal carcinoma, but subsequent randomized controlled trials found that adjuvant treatments such as cisplatin and fluorouracil, gemcitabine and cisplatin failed to improve survival and were toxic Therefore, the clinical application of adjuvant chemotherapy is gradually decreasing
.
However, the publication of the results of this trial is expected to rewrite the NCCN guidelines for adjuvant treatment of high-risk nasopharyngeal carcinoma
.
In an editorial published in the same journal, Professor Robert Kerbel from the University of Toronto in Canada spoke highly of this study, believing that this new model of maintenance therapy can change clinical practice and bring survival benefits to patients after high-intensity radiotherapy and chemotherapy.
An anti-cancer model that is easily accessible and can benefit the grassroots has also been established
.
Follow-up exploration This trial did not clarify the optimal duration of capecitabine rhythm chemotherapy
.
Since nasopharyngeal carcinoma has the highest risk of recurrence within 2 years after radiotherapy and chemotherapy, it is unclear whether the intensity of treatment for 1 year is sufficient
.
In addition, pre-clinical studies have shown that rhythm chemotherapy has an immunomodulatory effect, so it may play a synergistic effect with immunotherapy
.
A recently published phase 2 trial of pembrolizumab, bevacizumab, and cyclophosphamide rhythm chemotherapy in the treatment of recurrent ovarian cancer proved that the clinical benefit rate of this therapy can reach 95%
.
Therefore, the author is looking forward to the future research of rhythm chemotherapy combined with immunotherapy for high-risk nasopharyngeal carcinoma
.
Sotoracib treatment of lung cancer with KRAS p.
G12C mutation This article was published online on June 4, 2021 in NEJM
.
For details, see "CodeBreaK100: The Triumph of Precision Medicine and Innovative Design | Sotorasib Treats KRAS G12C Advanced NSCLC"
.
Olapali adjuvant therapy for BRCA1 or BRCA2 mutant breast cancer patients.
This article was published online on June 3, 2021 in NEJM
.
Professor Shao Zhimin from the Cancer Hospital of Fudan University is the co-author
.
Among breast cancer patients, approximately 5% of patients carry pathogenic or possibly pathogenic variants of the BRCA1 or BRCA2 germ cell line
.
Based on the mechanism of action of olaparib, the authors conducted a phase 3, double-blind, randomized trial to evaluate the adjuvant treatment of olaparib in breast cancer patients with BRCA1 or BRCA2 germ cell line pathogenic or possibly pathogenic variants.
Efficacy and safety
.
The enrolled early breast cancer patients were randomly assigned to receive oral olaparib or placebo for 1 year
.
The primary endpoint is the survival rate without invasive disease
.
At a median follow-up of 2.
5 years, an event-driven pre-interim analysis was performed.
The results showed that the 3-year survival rate without invasive disease in the olaparib group was 8.
8% higher than that in the placebo group, and the 3-year survival rate without distant disease It was 7.
1 percentage points higher than the placebo group
.
The number of deaths in the olaparib group was less than in the placebo group
.
The safety data are consistent with the known side effects of olaparib
.
The authors believe that in high-risk HER2-negative early breast cancer patients with BRCA1 or BRCA2 germ cell line mutations, adjuvant treatment with olaparib for 1 year can significantly reduce the risk of recurrence or distant metastasis, and systemic therapy is selected for early breast cancer patients When planning, BRCA1 or BRCA2 detection is extremely important
.
Isartuximab, Carfilzomib and Dexamethasone in the Treatment of Relapsed Multiple Myeloma This article was published online in Lancet on June 4, 2021
.
Although the treatment of multiple myeloma is progressing rapidly, it is still incurable
.
When the disease recurs, the choice of treatment plan should consider the degree and duration of remission, previous drug exposure and drug resistance
.
Isartuximab is an anti-CD38 monoclonal antibody.
Preclinical studies have shown that the combination of this drug with immunomodulators and proteasome inhibitors can exert a synergistic anti-myeloma effect
.
Carfilzomib is a second-generation proteasome inhibitor, and its combined treatment with dexamethasone is more effective than bortezomib combined with dexamethasone in the treatment of relapsed or refractory multiple myeloma
.
In this multi-center, open-label, phase 3 trial, the authors randomized relapsed or refractory multiple myeloma who had received median 2 line therapy to receive ixartuximab, carfilzomib and Combination therapy with dexamethasone or only treatment with carfilzomib and dexamethasone
.
The primary endpoint is progression-free survival
.
After a median follow-up of 20.
7 months, the median progression-free survival (not reached) of the ixatuximab group was significantly better than that of the control group (19.
15 months)
.
Each subgroup showed the advantage of progression-free survival
.
The complete remission rates of the ixatuximab group and the control group were 40% and 28%, respectively, while the negative rates of minimal residual disease were 30% and 13%, respectively
.
The author believes that for patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of treatment, the combination of Sartuximab, Carfilzomib and Dexamethasone can significantly improve progression-free survival and enhance the degree of remission.
.
Nivolumab combined with chemotherapy as the first-line treatment of advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer.
This article was published online in The Lancet on June 5, 2021
.
Professor Lin Lin from Peking University Cancer Hospital and Professor Liu Tianshu from Zhongshan Hospital Affiliated to Fudan University are co-authors
.
For patients with advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer and HER2-negative tumors, platinum and fluorouracil drugs are still the main adjuvant therapy drugs
.
But the median OS is only about 11 months
.
This international multicenter trial compared the efficacy of nivolumab combined with chemotherapy and chemotherapy alone on advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer
.
The results showed that among patients with PD-L1 composite positive score (CPS) ≥ 5, the median OS of the nivolumab combined with chemotherapy group was 14.
4 months, and that of chemotherapy alone group was 11.
1 months; the median PFS were respectively 7.
7 months and 6.
0 months
.
In patients with PD-L1 CPS≥1, OS and PFS were also significantly better than the control group
.
No new safety events were found in the trial, and the health-related quality of life of the two groups was similar
.
Previous trials compared the efficacy of pembrolizumab combined with chemotherapy in advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer, with mixed results
.
The trial of pembrolizumab failed to prove that combination therapy can improve OS
.
Therefore, nivolumab is the first immunotherapy drug that has been proven to improve OS in advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer
.
KTE-X19 for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia The recurrence rate of adult B-cell acute lymphoblastic leukemia after treatment is as high as 40%~50%, and the 1-year survival rate after the first rescue treatment is only 26%
.
Although new drugs can improve the disease remission rate, the median OS is still no more than 8 months
.
Bijal Shah and others conducted a multicenter phase 2 clinical trial to evaluate the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T cells in the treatment of relapsed or refractory acute lymphoblastic leukemia
.
The primary endpoints are complete remission rate and bone marrow remission with incomplete recovery rate of blood picture
.
A total of 71 patients were enrolled in the trial, of which 55 were treated with the study product (KTE-X19)
.
39 cases (71%) achieved complete remission or bone marrow remission with incomplete recovery of blood picture
.
The median OS was 18.
2 months, and the median OS had not yet been reached in patients who achieved complete remission or bone marrow remission with incomplete blood recovery
.
The authors also found that CAR T cell expansion is associated with disease remission or toxicity
.
The author believes that patients with relapsed or refractory acute lymphoblastic leukemia receiving KTE-X19 treatment can obtain a higher rate of complete remission or bone marrow remission with incomplete blood recovery, and may have long-term survival benefits
.
Copyright information This article was translated, written or commissioned by the "NEJM Frontiers of Medicine" jointly created by the Jiahui Medical Research and Education Group (J-Med) and the "New England Journal of Medicine" (NEJM)
.
The Chinese translation of the full text and the included diagrams are exclusively authorized by the NEJM Group
.
If you need to reprint, please leave a message or contact nejmqianyan@nejmqianyan.
cn
.
Unauthorized translation is an infringement, and the copyright owner reserves the right to pursue legal liabilities
.
It is also said that JAMA and BMJ of the four major medical journals have not yet published papers
.
Among them, Lancet today announced the results of a phase 3 randomized controlled clinical trial led by Professor Ma Jun from the Cancer Center Affiliated to Sun Yat-sen University and participated by 14 hospitals in China
.
This trial studied the efficacy and safety of capecitabine rhythm adjuvant chemotherapy for patients with locally advanced nasopharyngeal carcinoma who received radical concurrent radiotherapy and chemotherapy
.
The results showed that receiving capecitabine rhythm chemotherapy for this type of nasopharyngeal cancer patients can significantly improve the 3-year tumor-free survival rate and overall survival rate, and the safety is better
.
The total cost of capecitabine maintenance treatment for one year is less than 5,000 yuan, and it is oral treatment, which is convenient to use and has a high degree of patient acceptance.
It is conducive to promotion to the grassroots.
Its cost performance and popularity are self-evident
.
During the 2019 ASCO annual meeting, NEJM published another nasopharyngeal cancer clinical trial by Ma Jun's team, namely the use of gemcitabine combined with cisplatin (GP) induction chemotherapy before concurrent radiotherapy and chemotherapy
.
We have invited Dr.
Zhang Yuan, the first author of the paper, and Prof.
Jun Ma, the last author, to introduce the research and publication experience (see "It is less than 1 month from submission to NEJM acceptance.
Teachers and students will tell you how this is done.
" ")
.
The editorial department of "NEJM Frontiers in Medicine" compiled the main points of these 6 papers for readers
.
Capecitabine beat adjuvant treatment of locally advanced nasopharyngeal carcinoma has a significant effect.
Looking for clues in failure.
For locally advanced nasopharyngeal carcinoma, especially the subgroup of patients with poor prognostic factors, concurrent radiotherapy and chemotherapy is the main method to cure the disease
.
However, in patients with complete clinical remission, about 30% of patients will have local recurrence or distant metastasis
.
Therefore, finding an effective and safe adjuvant treatment plan is extremely important for these patients
.
Previous studies have selected the classic cisplatin and fluorouracil regimen or the emerging gemcitabine combined with cisplatin regimen as adjuvant chemotherapy drugs
.
However, the results of both studies showed that these adjuvant chemotherapy regimens failed to improve patient survival
.
Ma Jun and others analyzed the shortcomings of previous studies.
They believe that due to the toxicity of previous adjuvant chemotherapy, patients who have received radical radiotherapy and chemotherapy are difficult to tolerate, resulting in a completion rate of only 40% to 60% of adjuvant chemotherapy.
This may be due to the previous adjuvant chemotherapy.
Reasons why chemotherapy is ineffective
.
Capecitabine is a classic chemotherapeutic drug that has been used clinically for many years.
Unlike traditional chemotherapy that uses the maximum tolerated dose to treat tumors, capecitabine can be administered for a long time by low-dose, long-term oral administration of "beating" Maintained at a relatively low blood drug concentration, which can reduce toxic side effects while continuing to fight tumors, and is especially suitable for maintenance treatment of patients after radiotherapy and chemotherapy
.
Inspired by this, Sun Yat-sen University took the lead in launching a Phase 3 clinical trial of capecitabine rhythm chemotherapy for adjuvant treatment of locally advanced nasopharyngeal carcinoma
.
Significant curative effect and outstanding advantages.
This is a multi-center, open-label, parallel group, randomized controlled trial.
A total of 406 patients with locally advanced nasopharyngeal carcinoma were enrolled.
The patients were randomly assigned to the adjuvant treatment group (capecitabine beats).
Chemotherapy group) and clinical observation group (standard treatment group)
.
Patients in the standard treatment group did not receive adjuvant treatment, only routine review
.
Patients in the capecitabine rhythm chemotherapy group received low-dose capecitabine (650 mg/m2, twice a day) for one year
.
The primary endpoint of the trial is the 3-year failure-free survival (FFS), which is the time from randomization to tumor recurrence, metastasis, or death from any cause
.
Secondary endpoints include overall survival, survival without distant metastasis, survival without local recurrence, safety, and quality of life
.
The test results showed that after a median follow-up of 38 months, there were 29 recurrences or deaths in the capecitabine rhythm chemotherapy group (14%) and 53 cases (53%) in the standard treatment group
.
In the intention-to-treat group, the cumulative incidence of disease recurrence or death in the capecitabine rhythm chemotherapy group was 16.
6%, while that in the standard treatment group was 29.
0%
.
The 3-year tumor-free survival rate of the capecitabine-beat chemotherapy group was 85.
3% (95% CI, 80.
4%~90.
6%), while the standard treatment group was 75.
7% (95% CI, 69.
9~81.
9); disease recurrence or The hazard ratio for death was 0.
5 (95% CI, 0.
32 to 0.
79)
.
The 3-year overall survival rate of the capecitabine chemotherapy group (93.
3%; 95% CI, 89.
7%-97.
1%) was also significantly higher than that of the standard treatment group (88.
6%; 95% CI, 84.
2%-93.
2%), and the risk of death The ratio was 0.
44 (95% CI, 0.
22 to 0.
88)
.
At the same time, the 3-year survival rate without distant metastasis and survival rate without local recurrence in the capecitabine beat chemotherapy group were higher than those in the standard treatment group
.
The author also conducted a subgroup analysis based on tumor stage, lymph node stage, and disease stage
.
The results showed that the tumor-free survival rate of the capecitabine rhythm chemotherapy group was higher than that of the standard treatment group in each subgroup
.
The author also specifically pointed out that regardless of whether the patient has received induction chemotherapy, the efficacy of the capecitabine rhythm chemotherapy group is better than that of the standard treatment group
.
Controllable safety In terms of safety, the incidence of grade 1 or grade 2 adverse events in the capecitabine rhythm chemotherapy group was 73%, and that in the standard treatment group was 51%
.
The incidence of grade 3 adverse events in the two groups was 17% and 6%, respectively
.
The most common adverse event in the capecitabine rhythm chemotherapy group was hand-foot syndrome (58%), of which 18% were grade 3 adverse events
.
The adverse events of the blood system include anemia (35%) and leukopenia (27%)
.
Other common adverse events include fatigue (27%) and nausea (22%)
.
However, most of the adverse events in the capecitabine rhythm chemotherapy group were grade 1 or 2, and with the exception of hand-foot syndrome, the incidence of grade 3 or 4 adverse events was similar in the two groups
.
No serious adverse events were reported in either group
.
The authors also used the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire to compare the quality of life of the two trial participants
.
The results found that the scores of the two groups at baseline were similar; and during the treatment period, the range of changes in the scores from the baseline had no clinical significance
.
This shows that capecitabine beat chemotherapy did not significantly affect the quality of life of patients
.
Precisely because of its good safety, although some patients suspended treatment or reduced their dose due to adverse events, 74% of patients in the rhythm chemotherapy group completed the one-year planned treatment, and the relative dose intensity of capecitabine reached 98.
1%
.
It is expected to rewrite the guidelines.
The significance of this study is that the authors confirmed for the first time in a phase 3 randomized controlled trial that capecitabine rhythm chemotherapy adjuvant treatment of high-risk locally advanced nasopharyngeal carcinoma can improve the survival rate of patients
.
The NCCN guidelines used concurrent chemoradiation combined with adjuvant chemotherapy as the standard treatment for locally advanced nasopharyngeal carcinoma, but subsequent randomized controlled trials found that adjuvant treatments such as cisplatin and fluorouracil, gemcitabine and cisplatin failed to improve survival and were toxic Therefore, the clinical application of adjuvant chemotherapy is gradually decreasing
.
However, the publication of the results of this trial is expected to rewrite the NCCN guidelines for adjuvant treatment of high-risk nasopharyngeal carcinoma
.
In an editorial published in the same journal, Professor Robert Kerbel from the University of Toronto in Canada spoke highly of this study, believing that this new model of maintenance therapy can change clinical practice and bring survival benefits to patients after high-intensity radiotherapy and chemotherapy.
An anti-cancer model that is easily accessible and can benefit the grassroots has also been established
.
Follow-up exploration This trial did not clarify the optimal duration of capecitabine rhythm chemotherapy
.
Since nasopharyngeal carcinoma has the highest risk of recurrence within 2 years after radiotherapy and chemotherapy, it is unclear whether the intensity of treatment for 1 year is sufficient
.
In addition, pre-clinical studies have shown that rhythm chemotherapy has an immunomodulatory effect, so it may play a synergistic effect with immunotherapy
.
A recently published phase 2 trial of pembrolizumab, bevacizumab, and cyclophosphamide rhythm chemotherapy in the treatment of recurrent ovarian cancer proved that the clinical benefit rate of this therapy can reach 95%
.
Therefore, the author is looking forward to the future research of rhythm chemotherapy combined with immunotherapy for high-risk nasopharyngeal carcinoma
.
Sotoracib treatment of lung cancer with KRAS p.
G12C mutation This article was published online on June 4, 2021 in NEJM
.
For details, see "CodeBreaK100: The Triumph of Precision Medicine and Innovative Design | Sotorasib Treats KRAS G12C Advanced NSCLC"
.
Olapali adjuvant therapy for BRCA1 or BRCA2 mutant breast cancer patients.
This article was published online on June 3, 2021 in NEJM
.
Professor Shao Zhimin from the Cancer Hospital of Fudan University is the co-author
.
Among breast cancer patients, approximately 5% of patients carry pathogenic or possibly pathogenic variants of the BRCA1 or BRCA2 germ cell line
.
Based on the mechanism of action of olaparib, the authors conducted a phase 3, double-blind, randomized trial to evaluate the adjuvant treatment of olaparib in breast cancer patients with BRCA1 or BRCA2 germ cell line pathogenic or possibly pathogenic variants.
Efficacy and safety
.
The enrolled early breast cancer patients were randomly assigned to receive oral olaparib or placebo for 1 year
.
The primary endpoint is the survival rate without invasive disease
.
At a median follow-up of 2.
5 years, an event-driven pre-interim analysis was performed.
The results showed that the 3-year survival rate without invasive disease in the olaparib group was 8.
8% higher than that in the placebo group, and the 3-year survival rate without distant disease It was 7.
1 percentage points higher than the placebo group
.
The number of deaths in the olaparib group was less than in the placebo group
.
The safety data are consistent with the known side effects of olaparib
.
The authors believe that in high-risk HER2-negative early breast cancer patients with BRCA1 or BRCA2 germ cell line mutations, adjuvant treatment with olaparib for 1 year can significantly reduce the risk of recurrence or distant metastasis, and systemic therapy is selected for early breast cancer patients When planning, BRCA1 or BRCA2 detection is extremely important
.
Isartuximab, Carfilzomib and Dexamethasone in the Treatment of Relapsed Multiple Myeloma This article was published online in Lancet on June 4, 2021
.
Although the treatment of multiple myeloma is progressing rapidly, it is still incurable
.
When the disease recurs, the choice of treatment plan should consider the degree and duration of remission, previous drug exposure and drug resistance
.
Isartuximab is an anti-CD38 monoclonal antibody.
Preclinical studies have shown that the combination of this drug with immunomodulators and proteasome inhibitors can exert a synergistic anti-myeloma effect
.
Carfilzomib is a second-generation proteasome inhibitor, and its combined treatment with dexamethasone is more effective than bortezomib combined with dexamethasone in the treatment of relapsed or refractory multiple myeloma
.
In this multi-center, open-label, phase 3 trial, the authors randomized relapsed or refractory multiple myeloma who had received median 2 line therapy to receive ixartuximab, carfilzomib and Combination therapy with dexamethasone or only treatment with carfilzomib and dexamethasone
.
The primary endpoint is progression-free survival
.
After a median follow-up of 20.
7 months, the median progression-free survival (not reached) of the ixatuximab group was significantly better than that of the control group (19.
15 months)
.
Each subgroup showed the advantage of progression-free survival
.
The complete remission rates of the ixatuximab group and the control group were 40% and 28%, respectively, while the negative rates of minimal residual disease were 30% and 13%, respectively
.
The author believes that for patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of treatment, the combination of Sartuximab, Carfilzomib and Dexamethasone can significantly improve progression-free survival and enhance the degree of remission.
.
Nivolumab combined with chemotherapy as the first-line treatment of advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer.
This article was published online in The Lancet on June 5, 2021
.
Professor Lin Lin from Peking University Cancer Hospital and Professor Liu Tianshu from Zhongshan Hospital Affiliated to Fudan University are co-authors
.
For patients with advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer and HER2-negative tumors, platinum and fluorouracil drugs are still the main adjuvant therapy drugs
.
But the median OS is only about 11 months
.
This international multicenter trial compared the efficacy of nivolumab combined with chemotherapy and chemotherapy alone on advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer
.
The results showed that among patients with PD-L1 composite positive score (CPS) ≥ 5, the median OS of the nivolumab combined with chemotherapy group was 14.
4 months, and that of chemotherapy alone group was 11.
1 months; the median PFS were respectively 7.
7 months and 6.
0 months
.
In patients with PD-L1 CPS≥1, OS and PFS were also significantly better than the control group
.
No new safety events were found in the trial, and the health-related quality of life of the two groups was similar
.
Previous trials compared the efficacy of pembrolizumab combined with chemotherapy in advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer, with mixed results
.
The trial of pembrolizumab failed to prove that combination therapy can improve OS
.
Therefore, nivolumab is the first immunotherapy drug that has been proven to improve OS in advanced gastric cancer, gastroesophageal junction cancer or esophageal cancer
.
KTE-X19 for the treatment of relapsed or refractory adult B-cell acute lymphoblastic leukemia The recurrence rate of adult B-cell acute lymphoblastic leukemia after treatment is as high as 40%~50%, and the 1-year survival rate after the first rescue treatment is only 26%
.
Although new drugs can improve the disease remission rate, the median OS is still no more than 8 months
.
Bijal Shah and others conducted a multicenter phase 2 clinical trial to evaluate the efficacy and safety of anti-CD19 chimeric antigen receptor (CAR) T cells in the treatment of relapsed or refractory acute lymphoblastic leukemia
.
The primary endpoints are complete remission rate and bone marrow remission with incomplete recovery rate of blood picture
.
A total of 71 patients were enrolled in the trial, of which 55 were treated with the study product (KTE-X19)
.
39 cases (71%) achieved complete remission or bone marrow remission with incomplete recovery of blood picture
.
The median OS was 18.
2 months, and the median OS had not yet been reached in patients who achieved complete remission or bone marrow remission with incomplete blood recovery
.
The authors also found that CAR T cell expansion is associated with disease remission or toxicity
.
The author believes that patients with relapsed or refractory acute lymphoblastic leukemia receiving KTE-X19 treatment can obtain a higher rate of complete remission or bone marrow remission with incomplete blood recovery, and may have long-term survival benefits
.
Copyright information This article was translated, written or commissioned by the "NEJM Frontiers of Medicine" jointly created by the Jiahui Medical Research and Education Group (J-Med) and the "New England Journal of Medicine" (NEJM)
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