​BMJ: Pathological complete remission should not be used as the primary endpoint of breast cancer neoadjuvant treatment studies

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Key points: BMJ: Complete pathological remission should not be used as the primary endpoint of neoadjuvant trials for breast cancer.
The Lancet: Abiraterone + prednisone should be used as high-risk non-metastatic prostate New standard therapy for cancer New drug: "first-in-class" ADC Vibotuzumab declared for marketing New drug: CD3/CD19/CD20 trispecific antibody approved Clinical 01BMJ: Complete pathological remission should not be used as a neoadjuvant for breast cancer The primary endpoint of the trial recently, a systematic review and meta-analysis evaluating pathological complete response (pCR) as a surrogate endpoint in a neoadjuvant randomized clinical trial of early breast cancer was published in the top journal BMJ
.

The results show that in clinical trials, pCR cannot be used as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS), so it should not be used as the primary endpoint of clinical trials for neoadjuvant therapy for early breast cancer
.

Screenshot of the journal’s official website.
The study analyzed randomized clinical trials of neoadjuvant treatment of breast cancer with chemotherapy alone or in combination with other treatments (including anti-HER2 drugs, targeted therapy, anti-angiogenesis drugs, bisphosphonates and immune checkpoint inhibitors).
The trial explored the association between pCR as a surrogate endpoint and DFS and OS
.

The study performed a weighted regression analysis on the log-transformed treatment effect estimates (risk ratio of DFS, OS, HR; relative risk of pCR, RR), and used the coefficient of determination (R2) to quantify the correlation
.

In addition, the study also evaluated the surrogate threshold effect (the minimum pCR RR value necessary to be able to predict the existence of a non-zero effect with the HR of DFS or OS)
.

A total of 54 randomized clinical trials were included in the analysis, covering 32,611 patients
.

A weak correlation was observed between the log (RR) of pCR and the log (HR) of DFS (R2=0.
14, 95%CI 0.
00-0.
29) and OS (R2=0.
08, 95%CI 0.
00-0.
22)
.

Similar results were found in all subgroups evaluated (regardless of the definition of pCR, the type of treatment in the experimental group, and the biological characteristics of the disease)
.

The replacement threshold effect of DFS is 5.
19, and OS cannot be estimated
.

In addition, 1) exclude small trials (enrolled <200 patients), 2) exclude trials with a shorter median follow-up time (<24 months), and 3) replace the relative risk of pCR with the absolute difference in the pCR rate for these three sensitive Consistent conclusions were found in the sexual analysis
.

02The Lancet: Abiraterone + prednisone should be used as the new standard therapy for high-risk non-metastatic prostate cancer.
(PC) The meta-analysis of the Phase III study was published in The Lancet
.

The results show that for men with high-risk non-metastatic PC, compared with androgen deprivation therapy (ADT) alone, combined therapy can significantly improve the metastasis-free survival rate.
Therefore, abiraterone acetate combined with prednisone should be a new strategy for this population.
Standard treatment method
.

Screenshot of the journal’s official website.
Men with high-risk non-metastatic PC received ADT for 3 years (usually combined with radiotherapy)
.

The researchers analyzed new data from two randomized controlled phase III trials completed in a multi-arm, multi-stage platform agreement to evaluate the efficacy of abiraterone combined with prednisone or further combined with enzalutamide in this patient population
.

In both trials, patients received ADT or oral abiraterone acetate (1000 mg/day) and prednisone (5 mg/day; combination therapy group)
.

In the second trial without overlapping controls, the combination treatment group also received enzalutamide (160 mg orally per day)
.

The duration of ADT treatment is 3 years, and the combined treatment group is 2 years until the disease progresses
.

The primary endpoint of this meta-analysis is metastasis-free survival
.

Secondary endpoints are OS, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival (PFS), and toxicity and adverse events
.

From November 15, 2011 to March 31, 2016, 1974 patients were randomly assigned to receive treatment with a median follow-up of 72 months (60-84 months).
There were 180 cases of metastasis-free survival in the combined treatment group.
The group is 306 cases
.

The metastasis-free survival of the combination treatment group (median not reached, IQR NE–NE) was significantly longer than that of the control group (not reached, 97–NE months; HR 0.
53; 95% CI 0.
44–0.
64; p<0.
0001)
.

The 6-year metastasis-free survival rate of the combined treatment group was 82% (95% CI 79%-85%), and the control group was 69% (95% CI 66%-72%)
.

Compared with abiraterone acetate alone, when both enzalutamide and abiraterone acetate were administered, there was no evidence that there was a difference in metastasis-free survival (interaction HR 1.
02; 95% CI 0.
70–1.
50; p=0.
91)
.

OS HR between the two groups was 0.
60 (95%CI 0.
48-0.
73; p<0.
0001), prostate cancer-specific survival rate HR was 0.
49 (95%CI 0.
37-0.
65; p<0.
0001), no biochemical failure-survival rate HR was 0.
39 (95%CI 0.
33-0.
47; p<0.
0001), PFS HR was 0.
44 (95%CI 0.
36-0.
54; p<0.
0001), the combination treatment group was significantly better than the control group
.

In the combination treatment group and the control group of the two trials, the proportions of adverse events in the first 24 months were 37% vs 29% and 58% vs 32%, respectively
.

03 New drug: "first-in-class" ADC Vibrotuzumab declared for listing.
The official website of the Center for Drug Evaluation (CDE) of the State Drug Administration of China revealed that Roche has submitted four Vibo for injection in China Listing application for Touzumab
.

Public information shows that vedotin (polatuzumab vedotin) is a “first-in-class” antibody conjugate drug (ADC) targeting CD79b.
It has been approved for marketing in more than 60 countries and regions around the world.
Relapsed or refractory diffuse large B-cell lymphoma
.

04New drug: CD3/CD19/CD20 trispecific antibody was approved for clinical use On December 29, vPro announced that the clinical trial application for trispecific antibody BR110 (CMG1A46) has been approved by the National Medical Products Administration (NMPA).
It is intended for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma
.

This clinical approval also makes BR110 the world's first clinically approved CD3/CD19/CD20 trispecific antibody
.

Reference: [1].
Conforti F, et al.
BMJ 2021; 375 :e066381 doi:10.
1136/bmj-2021-066381.
https:// ].
Attard G, et al.
Lancet.
2021 Dec 23:S0140-6736(21)02437-5.
doi: 10.
1016/S0140-6736(21)02437-5.
https:// lancet/article/PIIS0140-6736(21)02437-5/fulltext[3].
https://mp.
weixin.
qq.
com/s/1FVqY927hL9ExDNZGZhfWw[4].
https://mp.
weixin.
qq.
com/ s/Om9CvUPGKAi9iCvSxnTmog