IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.
IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer.
- 2024
Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006
BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials. Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell >=1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure.
English
0923-7534
S0923-7534(24)00107-8 [pii]
*Antibodies, Monoclonal, Humanized
*Antineoplastic Combined Chemotherapy Protocols
*Gemcitabine
*Neoplasm Recurrence, Local
*Triple Negative Breast Neoplasms
Adult
Aged
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
B7-H1 Antigen/ai [Antagonists & Inhibitors]
B7-H1 Antigen/me [Metabolism]
Capecitabine/ad [Administration & Dosage]
Carboplatin/ad [Administration & Dosage]
Deoxycytidine/aa [Analogs & Derivatives]
Deoxycytidine/ad [Administration & Dosage]
Deoxycytidine/tu [Therapeutic Use]
Double-Blind Method
Female
Humans
Immune Checkpoint Inhibitors/ad [Administration & Dosage]
Immune Checkpoint Inhibitors/ae [Adverse Effects]
Middle Aged
Neoplasm Recurrence, Local/dt [Drug Therapy]
Neoplasm Recurrence, Local/pa [Pathology]
Progression-Free Survival
Triple Negative Breast Neoplasms/dt [Drug Therapy]
Triple Negative Breast Neoplasms/pa [Pathology]--Automated
Associate Dean for Research Development
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006
BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials. Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell >=1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure.
English
0923-7534
S0923-7534(24)00107-8 [pii]
*Antibodies, Monoclonal, Humanized
*Antineoplastic Combined Chemotherapy Protocols
*Gemcitabine
*Neoplasm Recurrence, Local
*Triple Negative Breast Neoplasms
Adult
Aged
Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
B7-H1 Antigen/ai [Antagonists & Inhibitors]
B7-H1 Antigen/me [Metabolism]
Capecitabine/ad [Administration & Dosage]
Carboplatin/ad [Administration & Dosage]
Deoxycytidine/aa [Analogs & Derivatives]
Deoxycytidine/ad [Administration & Dosage]
Deoxycytidine/tu [Therapeutic Use]
Double-Blind Method
Female
Humans
Immune Checkpoint Inhibitors/ad [Administration & Dosage]
Immune Checkpoint Inhibitors/ae [Adverse Effects]
Middle Aged
Neoplasm Recurrence, Local/dt [Drug Therapy]
Neoplasm Recurrence, Local/pa [Pathology]
Progression-Free Survival
Triple Negative Breast Neoplasms/dt [Drug Therapy]
Triple Negative Breast Neoplasms/pa [Pathology]--Automated
Associate Dean for Research Development
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial