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| Ref Type | Journal Article | ||||||||||||
| PMID | (38755096) | ||||||||||||
| Authors | Dent R, André F, Gonçalves A, Martin M, Schmid P, Schütz F, Kümmel S, Swain SM, Bilici A, Loirat D, Villalobos Valencia R, Im SA, Park YH, De Laurentis M, Colleoni M, Guarneri V, Bianchini G, Li H, Kirchmayer Machackova Z, Mouta J, Deurloo R, Gan X, Fan M, Mani A, Swat A, Cortés J | ||||||||||||
| Title | 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. | ||||||||||||
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| Abstract Text | 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.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.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.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. | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| CD274 positive | triple-receptor negative breast cancer | no benefit | Atezolizumab + Carboplatin + Gemcitabine | Phase III | Actionable | In a Phase III trial (Impassion132), the addition of Tecentriq (atezolizumab) to Xeloda (capecitabine) or Paraplatin (carboplatin) plus Gemzar (gemcitabine) treatment did not improve efficacy in early relapsing, unresectable, advanced CD274 (PD-L1)-positive triple-negative breast cancer patients, with median overall survival of 12.1 vs. 11.2 mo (HR=0.93, p=0.59), median progression-free survival of 4.2 vs. 3.6 mo, and objective response rates of 40% (61/177) vs. 28% (45/177) (PMID: 38755096; NCT03371017). | 38755096 |
| CD274 positive | triple-receptor negative breast cancer | no benefit | Atezolizumab + Capecitabine | Phase III | Actionable | In a Phase III trial (Impassion132), the addition of Tecentriq (atezolizumab) to Xeloda (capecitabine) or Paraplatin (carboplatin) plus Gemzar (gemcitabine) treatment did not improve efficacy in early relapsing, unresectable, advanced CD274 (PD-L1)-positive triple-negative breast cancer patients, with median overall survival of 12.1 vs. 11.2 mo (HR=0.93, p=0.59), median progression-free survival of 4.2 vs. 3.6 mo, and objective response rates of 40% (61/177) vs. 28% (45/177) (PMID: 38755096; NCT03371017). | 38755096 |