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KEYNOTE-355

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer

Phase 3N = 847NCT02819518

Population
Previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer, centrally confirmed
Design
Randomised 2:1, double-blind, placebo-controlled phase 3 trial of pembrolizumab 200 mg every 3 weeks plus investigator-chosen chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) versus placebo plus chemotherapy. Dual primary endpoints PFS and OS in the PD-L1 CPS 10 or more, CPS 1 or more and ITT populations; the Lancet abstract describes hierarchical testing for PFS.
Primary endpoint
PFS, OS
Arms
  • Pembrolizumab plus chemotherapy (experimental, n = 566): Pembrolizumab 200 mg every 3 weeks plus nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin
  • Placebo plus chemotherapy (control, n = 281): Placebo plus nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin
People
Cortes J, KEYNOTE-355 Investigators
PFSHR 0.65 (95% CI 0.49–0.86)Δ median PFS+4.1 monthsPFSHR 0.74 (95% CI 0.61–0.90)Δ median PFS+2 monthsPFSHR 0.82 (95% CI 0.69–0.97)Δ median PFS+1.9 months
Show the numbers
Results reported for KEYNOTE-355
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
PFSPD-L1 CPS 10 or moreinterimmedian follow-up 25.9 monthsCortes 2020median 9.7 monthsmedian 5.6 monthsHR 0.65 (95% CI 0.49–0.86)P=0.0012One-sided P value; primary objective met per the abstract. Median follow-up 25.9 months (pembrolizumab-chemotherapy) and 26.3 months (placebo-chemotherapy).
PFSPD-L1 CPS 1 or moreinterimmedian follow-up 25.9 monthsCortes 2020median 7.6 monthsmedian 5.6 monthsHR 0.74 (95% CI 0.61–0.90)P=0.0014One-sided P value; reported as not significant under the hierarchical testing procedure.
PFSinterimmedian follow-up 25.9 monthsCortes 2020median 7.5 monthsmedian 5.6 monthsHR 0.82 (95% CI 0.69–0.97)Not tested (per the abstract).
OSPD-L1 CPS 10 or morefinalmedian follow-up 44.1 monthsCortes 2022median 23 monthsmedian 16.1 monthsHR 0.73 (95% CI 0.55–0.95)P=0.0185Two-sided P; criterion for significance met.
OSPD-L1 CPS 1 or morefinalmedian follow-up 44.1 monthsCortes 2022median 17.6 monthsmedian 16 monthsHR 0.86 (95% CI 0.72–1.04)P=0.1125Two-sided P; not significant.
OSfinalmedian follow-up 44.1 monthsCortes 2022median 17.2 monthsmedian 15.5 monthsHR 0.89 (95% CI 0.76–1.05)Significance not tested (per the abstract).
Results reported for KEYNOTE-355
EndpointAnalysisPembrolizumab plus chemotherapyPlacebo plus chemotherapyEffect
PFSPD-L1 CPS 10 or moreinterimmedian follow-up 25.9 monthsCortes 2020median 9.7 monthsmedian 5.6 monthsHR 0.65 (95% CI 0.49–0.86)P=0.0012One-sided P value; primary objective met per the abstract. Median follow-up 25.9 months (pembrolizumab-chemotherapy) and 26.3 months (placebo-chemotherapy).
PFSPD-L1 CPS 1 or moreinterimmedian follow-up 25.9 monthsCortes 2020median 7.6 monthsmedian 5.6 monthsHR 0.74 (95% CI 0.61–0.90)P=0.0014One-sided P value; reported as not significant under the hierarchical testing procedure.
PFSinterimmedian follow-up 25.9 monthsCortes 2020median 7.5 monthsmedian 5.6 monthsHR 0.82 (95% CI 0.69–0.97)Not tested (per the abstract).
OSPD-L1 CPS 10 or morefinalmedian follow-up 44.1 monthsCortes 2022median 23 monthsmedian 16.1 monthsHR 0.73 (95% CI 0.55–0.95)P=0.0185Two-sided P; criterion for significance met.
OSPD-L1 CPS 1 or morefinalmedian follow-up 44.1 monthsCortes 2022median 17.6 monthsmedian 16 monthsHR 0.86 (95% CI 0.72–1.04)P=0.1125Two-sided P; not significant.
OSfinalmedian follow-up 44.1 monthsCortes 2022median 17.2 monthsmedian 15.5 monthsHR 0.89 (95% CI 0.76–1.05)Significance not tested (per the abstract).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSPFSOSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.650.49–0.86
PFS0.740.61–0.9
PFS0.820.69–0.97
OS0.730.55–0.95
OS0.860.72–1.04
OS0.890.76–1.05
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%05101520Months (modelled)
  • Pembrolizumab plus chemotherapy (experimental)
  • Placebo plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumab plus chemotherapyPlacebo plus chemotherapy
0100.0%100.0%
665.1%47.6%
1242.4%22.6%
1827.6%10.8%
2418.0%5.1%
Illustrative — modelled from reported values, not trial data. PFS, interim.
0%25%50%75%100%051015Months (modelled)
  • Pembrolizumab plus chemotherapy (experimental)
  • Placebo plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPembrolizumab plus chemotherapyPlacebo plus chemotherapy
0100.0%100.0%
563.4%53.9%
1040.2%29.0%
1427.9%17.7%
1917.7%9.5%
Primary publication: Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828. PubMedDOI

Appears in

Sources

  1. Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817-1828.

    PubMedDOI

  2. Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2022;387(3):217-226.

    PubMedDOI