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ASCO 2021: Overview of Oral Abstracts for Metastatic Breast Cancer Special Session

 Last Update: 2021-06-10
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From June 4th to 8th, one of the largest events in global cancer research-the American Society of Clinical Oncology ( ASCO ) annual meeting will be held.

For more information, follow the ASCO special page of Metz Medicine: https://meeting.

Reporting Chair: Adam Brufsky, MD, PhD, NSABP/NRG Oncology and UPMC Hillman Cancer Center | Olwen Mary Hahn, MD, University of Chicago Medical Center

Report to the chairman:

Subject: Metastatic Breast Cancer

Subject: Breast Cancer

Abstract Introduction 1

The overall survival (OS ) of palbociclib (PAL ) + Fulvestrant ( FUL ) in hormone receptor positive (HR+ ), human epidermal growth factor receptor 2 negative (HER2- ) advanced breast cancer (ABC ) women : update Analysis of PALOMA-3

DOI: 10.

PALOMA-3 is a randomized, double-blind, placebo-controlled phase 3 study.

A total of 521 HR+/HER2– ABC patients (pts) had progressed in the previous endocrine therapy.

With the extension of follow-up time, the improvement of OS continued to be observed, and the hazard ratio was 0.

The latest OS status of the ITT population and each subgroup

Studies have shown that in HR+/HER2-ABC patients, the clinical significance of PAL+FUL on the improvement of OS is maintained for more than 6 years in the case of progress in the previous endocrine therapy.

Abstract Introduction 2

Postmenopausal patients (pts ) with HR+/HER2- advanced breast cancer (ABC ) receiving fulvestrant ( FUL ) ± Ribocinil (RIB ) in the Phase III MONALEESA-3 trial, the latest overall survival rate (OS )result

DOI: 10.

The Phase III MONALEESA-3 trial (NCT02422615) has demonstrated that in postmenopausal patients with HR+/HER2-ABC, RIB (a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i)) plus FUL and placebo Compared with (PBO) plus FUL as first-line (1L) or second-line (2L) treatment, OS has a significant improvement (median, less than VS.

At the time of the data cutoff (October 30, 2020), the median follow-up time was 56.

Studies have shown that in postmenopausal patients with HR+/HER2−ABC, after nearly 5 years of follow-up, the previously proven robust and clinically significant OS benefits of RIB + FUL compared with PBO + FUL are maintained.

Abstract introduction 3

Comparison of Dalpiciclib and placebo plus fulvestrant in HR+/HER2- advanced breast cancer (DAWNA-1) that have relapsed or progressed from previous endocrine therapy : a multicenter, randomized, phase 3 study

Xu Binghe, MD, PhD

National Cancer Center/National Cancer Research Center/Chinese Academy of Medical Sciences, Peking Union Medical College Medical Oncology Department

DOI: 10.

Dalpiciclib (SHR6390) is a new type of CDK4/6 inhibitor.

In this randomized, double-blind, phase 3 trial, patients with HR+/HER2− locally advanced or metastatic breast cancer (pts) were recruited who had relapsed or progressed from previous endocrine therapy.

Overall, 361 patients were randomized to receive dalp-fulv (n = 241) or PBO-fulv (n = 120).

The study reached the primary endpoint, showing that dalpiciclib plus fulvestrant can significantly improve PFS compared with placebo plus fulvestrant, and the safety is controllable.
Our findings support Dalpiciclib plus fulvestrant as a new treatment option for HR+/HER2-ABC patients who relapse or progress after receiving endocrine therapy.

Abstract Introduction 4

Trastuzumab plus endocrine therapy or chemotherapy as the first-line treatment for hormone receptor-positive and HER2- positive metastatic breast cancer: sysucc-002 randomized clinical trial

Yuan Zhongyu, Professor

Department of Oncology, Sun Yat-sen University Cancer Center

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1002

For hormone receptor-positive and HER2-positive metastatic breast cancer, there is no evidence to show which first-line treatment is better, whether it is anti-HER2 therapy plus endocrine therapy or anti-HER2 therapy plus chemotherapy.
This study aims to determine whether the efficacy of trastuzumab plus endocrine therapy is the same as that of trastuzumab plus chemotherapy, and the toxicity is reduced.

We conducted an open-label, non-inferiority, phase 3, randomized controlled trial in 9 hospitals in China.
Patients with hormone receptor-positive and HER2-positive histologically confirmed advanced breast cancer were randomly assigned (1:1) to receive trastuzumab plus chemotherapy (CT group) or endocrine therapy (ET group).
The primary endpoint is progression-free survival, and the non-inferiority upper limit of the hazard ratio (HR) is 1.
35.

From September 16, 2013 to December 28, 2019, 392 patients were enrolled and randomly assigned to receive trastuzumab plus endocrine therapy (n = 196) or trastuzumab plus chemotherapy (n = 196) .
In the intention-to-treat population, the median PFS of the CT group was 14.
8 months (95%CI was 12.
8-16.
8), and the ET group was 19.
2 months (95%CI was 16.
7-21.
7) (HR 0.
88, 95%CI was 0.
71-1.
09; Pnon-inferiority<0.
0001).
Compared with the ET group, the frequency of toxic reactions in the CT group was significantly higher, including: leukopenia (98 [50%] vs 13 [6.
6%]), nausea (93 [47%] vs 24 [12%]), Fatigue (47 [24%] vs 31 [16%]), vomiting (45 [23%] vs 12 [6%]), headache (65 [33%] vs 24 [12%]) and hair loss (125 [64 %] vs 8 [4%] ).
No patient died of treatment-related causes.

Studies have shown that in patients with hormone receptor-positive and HER2-positive metastatic breast cancer, trastuzumab plus endocrine therapy is not inferior to trastuzumab plus chemotherapy, and the toxicity is reduced.
Trastuzumab plus endocrine therapy can provide more convenient treatment and allow better treatment tolerance.

Abstract introduction 5

VERONICA 's results: a second-line/ third-line venettoque (VEN) + fulvestrant (F) and F alone in estrogen receptor (ER) -positive, HER2- negative, locally advanced or metastatic breast cancer A randomized phase II study of treatment .

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1004

For patients with ER-positive and HER2-negative MBC (pts), CDK4/6 inhibitor + endocrine therapy (ET) is the standard first-line treatment, and single-agent ET is considered for second-line treatment.
Nevertheless, most pts have made progress.
A new therapeutic target is the anti-apoptotic protein BCL2, which is overexpressed in 85% of primary ER-positive breast cancers.
VEN is a potent and selective BCL2 inhibitor, showing promising clinical activity in ER-positive and BCL2-positive MBC patients who have previously received ET.
We report the pre-specified primary and updated (for overall survival [OS]) analysis of VERONICA (NCT03584009), a phase II study of VEN + F and F in ER-positive, HER2-negative LA/MBC.

The patient is an ER-positive, HER2-negative LA/MBC female ≥18 years of age, who has received ≤2 ET treatments before, and has not received LA/MBC chemotherapy before, and the disease has recurred/progressed during/after CDK4/6 inhibitor treatment (Have received ≥8 weeks before).
Patients randomly choose VEN (oral; 800 mg per day) + F (intramuscular injection; 500 mg, on the 1st and 15th days of the first cycle; the first day of the subsequent 28-day cycle) or F at a 1:1 ratio.
And receive treatment until the disease progresses, unacceptable toxicity, withdrawal of consent, death, or the end of the scheduled study.
Patients were stratified according to the previous treatment line (1 vs 2) and BCL2 status (high vs low) in the LA/MBC environment.
The primary endpoint is the clinical benefit rate (CBR; complete response, partial response, and stable disease for ≥24 weeks).
Secondary endpoints included progression-free survival (PFS) and OS; safety and exploratory subgroup analyses were also performed.

In the main analysis (deadline: August 5, 2020), 103 patients were randomized (intention-to-treat [ITT] population).
The median ages of VEN + F group and F group were 58.
0 years and 59.
5 years, respectively.
The CBR between the two groups was similar (VEN + F: 11.
8% [n = 6/51; 95% confidence interval (CI) 4.
44–23.
87]; F: 13.
7% [7/51; 5.
70–26.
26]; risk difference: -1.
96% [95% CI -16.
86-12.
94]).
The median PFS in the VEN + F group was 2.
69 months (95% CI 1.
94-3.
71), while the F group was 1.
94 months (1.
84-3.
55) (stratified hazard ratio: 0.
94 [95% CI 0.
61-1.
45]).
The results of CBR and PFS were similar in the BCL2 high and low subgroups and the ITT population.
More grade 3-4 adverse events (AE) were observed in the VEN + F and F groups (n = 13/50 [26%] and 6/51 [11.
8%]).
The AEs observed with VEN + F are consistent with their individual safety characteristics.
In the updated analysis (deadline: October 22, 2020), the OS data is immature (35.
0% events/pt ratio); the median OS of the VEN + F group is 16.
99 months, while the F group has not reached (points).
Tier risk ratio: 2.
06 [1.
04–4.
09]).

From the main analysis, in patients with endocrine and CDK4/6 inhibitor refractory LA/MBC, VERONICA compared with F alone, the use of VEN + F did not show improved CBR or PFS.
Biomarker analysis is underway.

Abstract Introduction 6

Treatment-related side effects and perceptions of dose assessment for maintaining quality of life: results of an advocate-led survey of patients with metastatic breast cancer (MBC)

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1000

Metastatic breast cancer (MBC) is usually incurable, and most patients with MBC will receive treatment indefinitely.
Based on the results of clinical trials, patients usually start each new treatment with the recommended starting dose (RSD) on the FDA- approved label.
However, the patient's ability to tolerate RSD in the real world may be different from the clinical trial environment.
Although people recognize the importance of patient reporting, there is a lack of understanding of tolerability from the perspective of patients, and there is no assessment of patients' willingness to discuss individualized doses of MBC treatment.

FDA

Patient advocates from the "Patient-Centered Medication Initiative" distributed a confidential online survey to MBC patients through social media groups, organizational communications, and online support forums.
The survey was developed by patients and medical oncologists to determine the incidence and impact of treatment-related side effects of patients, the quality of patient-doctor communication, the management of side effects, and interest in alternatives to RSD or adverse side effects when starting new treatments .

management

1,221 MBC patients completed the investigation within 15 days.
The median of MBC treatment was 2.
5 lines (range 1-≥5), and 46% (n = 564) of patients were diagnosed with MBC within two years of the survey .
86% (n = 1,051) of patients reported experiencing at least one major treatment-related side effect, 20% (n = 213) of patients went to the emergency room/hospital, and 43% (n = 454) of patients missed at least One treatment.
Ninety-eight percent (n = 1,026) of patients with side effects discussed these side effects with their doctors, and 82% (n = 838) of patients received doctor's help.
The most common (not only) mitigation strategies are dose reduction (66%, n = 556) and prescription drugs (59%, n = 494).
Of the 556 patients who were given a reduction, 83% (n = 459) reported feeling better.
It is worth noting that 92% (n = 1,127) of patients expressed their willingness to discuss alternative doses with their doctors based on their personal characteristics and personal preferences.

diagnosis

Given that 86% of MBC patients have experienced at least one major treatment-related side effect, and 83% of patients have improved after reducing the dose, it is necessary to adopt innovative dose-related strategies to maintain quality of life.
A doctor-patient discussion that regularly evaluates the patient's physical characteristics and conditions can determine the correct dose for the patient at the beginning and after treatment, and most patients will accept this discussion.

Abstract Introduction 7

Tumor microenvironment (TME) and atezolizumab + nab- paclitaxel (A+nP) activity in metastatic triple-negative breast cancer (mTNBC) : IMpassion130

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1006

IMpassion130 is the first randomized phase 3 study to show the clinical benefit of cancer immunotherapy (CIT) on untreated PD-L1+ mTNBC.
In patients with more abundant immune TME, the efficacy of A + nP was observed to be enhanced compared with placebo (P) + nP, but only in PD-L1 IC+ patients (PD-L1 expressing immune cells in ≥1% of tumor areas; Emens JNCI 2021).
Although TNBC molecular subtypes and CD8 localization have prognostic effects in early TNBC, it is unclear whether these features are related to the benefit of CIT in mTNBC.
This exploratory analysis aims to determine the TME components related to the efficacy of A+nP in IMpassion130.

immunity

IHC is used to assess PD-L1 status (VENTANA SP142) and immunophenotype (inflammation/exclusion/desert per CD8 stroma/localization within tumor; Marithasan Nature 2018).
RNA-seq is used for molecular subtype analysis (Burstein CCR 2015) and pathway analysis (MSigDB Hallmark).
Cox regression is used to compare the PFS/OS between A + nP and P + nP, adjusted according to the previous taxanes and liver metabolites.

The sample classification and PD-L1 distribution are shown in the table.
In PD-L1 IC+ inflammatory and exclusion tumors, A+nP has improved PFS compared with P+nP, but the improvement of OS is limited to PD-L1 IC+ inflammatory tumors.
PD-L1 IC+ basal immune activation (BLIA) and immunosuppression (BLIS) subgroups have PFS benefits, but the OS benefit is limited to PD-L1 IC+BLIA subgroups.
In PD-L1 IC+ patients, pathway analysis found proliferation/DNA damage repair (feature of basal-like tumors) and angiogenesis /ER response (higher in intraluminal androgen receptor [LAR]/interstitial [MES] tumors) Respectively related to the improvement and reduction of PFS.

Blood vessel

PD-L1 IC+ immune inflammatory tumors and PD-L1 IC+ BLIA tumors show the highest CIT sensitivity, while LAR tumors may be resistant to CIT.
These data are worthy of further research and verification.

Abstract Introduction 8

Famitinib combined with carrelizumab plus albumin-bound paclitaxel as the first-line treatment for patients with immunomodulatory advanced triple-negative breast cancer (FUTURE-C-PLUS) : a prospective, one-arm, phase 2 study

Li Chen

Shanghai Cancer Center, Fudan University

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1007

Camrelizumab (anti-PD-1 antibody) and albumin-bound paclitaxel (nab-P) show promising antitumor activity in immunomodulatory (IM) subtype metastatic triple-negative breast cancer (TNBC) patients, and in severe patients 52.
6% of ORR was observed in patients who were pretreated in our previous Umbrella Trial (FUTURE).
Since anti-angiogenic agents are known to enhance the response to immune checkpoint inhibitors, we evaluated famitinib (a tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit), carrelizin Efficacy and safety of the new triple combination of anti-albumin-bound paclitaxel in patients with the following diseases: IM subtype advanced TNBC.

In this prospective, one-arm, phase 2 study, eligible patients were between 18-70 years of age and had locally advanced or metastatic TNBC with unresectable IM subtype.
IM subtype is defined as CD8+ by immunohistochemistry.
Eligible patients receive carrelizumab (200 mg iv, day 1, day 15, q4w) and nab-P (100 mg/m 2 iv, day 1, day 8, day 15, day 15) 4 weeks) and famitinib (20 mg orally every day, day 1-28, week 4).
Treatment continues until the disease progresses, the patient withdraws, or unacceptable toxic effects occur.
In the absence of intolerable toxicity, nab-P will be administered for at least 6 cycles.
The primary endpoint is the objective response rate based on RECIST v1.
1.
We explored predictive biomarkers using targeted sequencing with 484 genomes.

From October 2019 to October 2020, a total of 48 patients were recruited.
39 of 48 patients in the intention-to-treat population (81.
3%; 95% CI 70.
2%-92.
3%) and 39 of 46 patients (84.
8%; 95% CI 74.
4%-95.
2%) achieved confirmation Objective relief is in the population that meets the plan.
The median response time was 1.
8 months (95% CI 1.
8-2.
0 months).
The median follow-up time was 9.
0 months, and the data on progression-free survival (PFS) and duration of remission were immature.
Thirty patients (62.
5%) are still receiving study treatment.
The 9-month PFS rate was 60.
2% (95% CI, 43.
2% to 77.
3%).
Grade 3 or 4 adverse events were neutropenia (33.
3%), anemia (10.
4%), febrile neutropenia (10.
4%), thrombocytopenia (8.
3%), hypertension (4.
2%), Hypothyroidism (4.
2%), proteinuria (2.
1%), sepsis (2.
1%) and immune-related myocarditis (2.
1%).
6.
3% of patients had an adverse event that led to the discontinuation of any drug.
Two patients experienced serious adverse events related to treatment.
No deaths related to treatment were reported.
Biomarker analysis indicates that somatic mutation GSK3A may have the potential to predict response to immunotherapy.

The addition of famitinib to carrelizumab and albumin-bound paclitaxel as a first-line therapy has shown promising anti-tumor activity and has a controllable toxicity profile for patients with IM subtype advanced TNBC.
We are eagerly looking forward to the results of the ongoing randomized controlled trial FUTURE-SUPER (NCT 04395989).

Summary Introduction 9

A 3- week randomized multicenter trial of cabazitaxel and weekly paclitaxel chemotherapy in the first-line treatment of HER2- negative metastatic breast cancer (MBC)

DOI: 10.
1200/JCO.
2021.
39.
15_suppl.
1008

Paclitaxel is commonly used as a first-line chemotherapy drug for HER2-negative MBC.
However, due to the 21.
5-53.
7% remission rate and the significant risk of peripheral neuropathy, more effective and better tolerated chemotherapy (CCT) is needed.

This open-label randomized (1:1) phase 2 trial compared cabazitaxel (25 mg/m 2) for 6 cycles every 3 weeks and paclitaxel (80 mg/m 2) once a week for 18 weeks as the first-line CCT .
HER2-negative and physical status ≤1 patients are eligible.
Patients taking cabazitaxel receive GCSF prophylaxis .
The primary endpoint is progression-free survival (PFS), which requires 127 events to detect a hazard ratio (HR) of 0.
65 with an efficacy of 85%.
Secondary endpoints include objective response rate (ORR; RECIST 1.
1), response time (TTR), overall survival (OS), safety and tolerability, and quality of life (QoL).

prevention

Compared with weekly paclitaxel, 3 times a week cabazitaxel as first-line chemotherapy for HER2-negative MBC did not significantly improve PFS, although it has a lower risk of peripheral neuropathy and patients report better overall health outcomes.
Cabazitaxel is safe and well tolerated for MBC, and requires fewer hospital visits, which is an important consideration for the COVID pandemic and beyond.

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