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KEYNOTE-355: Pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer


Pembrolizumab ( Keytruda ) monotherapy has shown promising antitumor activity and manageable safety in patients with metastatic triple-negative breast cancer ( TNBC ) in KEYNOTE-012, -086 and -119.

KEYNOTE-355 has compared Pembrolizumab + chemotherapy versus placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic TNBC.

Patients with 6 months or more disease-free interval ( DFI ) were randomized 2:1 to Pembrolizumab + chemotherapy ( nab-Paclitaxel; Paclitaxel; or Gemcitabine / Carboplatin ) or placebo + chemotherapy for up to 35 administrations of Pembrolizumab / placebo or until progression / intolerable toxicity.

Patients were stratified by chemotherapy type ( taxane vs Gemcitabine / Carboplatin ), PD-L1 status ( CPS 1 or more vs less than 1 ), and prior (neo)adjuvant treatment with same-class chemotherapy ( yes versus no ).

Dual primary endpoints were: progression-free survival ( PFS ) ( RECIST v1.1, blinded independent central review ) and overall survival ( OS ) by tumor PD-L1 expression ( CPS greater than or equal to 10 and greater than or equal to 1 ) and in all patients.

As of December 11 2019, median follow-up was 17.5 months for Pembrolizumab + chemotherapy ( n=566 ) and 15.5 months for chemotherapy ( n=281 ).

Pembrolizumab + chemotherapy has significantly improved progression-free survival versus chemotherapy alone in patients with CPS greater than or equal to 10 tumors, meeting one of the protocol-defined primary objectives [ Pembro + Chemo ( n=220 ) vs Chemo ( n=103 ); median PFS: 9.7 vs 5.6 months; hazard ratio, HR=0.65 ].

Although the boundary for a statistically significant benefit of Pembrolizumab + chemotherapy in patients with CPS greater than or equal to 1 tumors was not met [ Pembro + Chemo ( n=425 ) vs Chemo ( n=211 ); median PFS: 7.6 vs 5.6 months; HR=0.74 ] and formal testing in intention-to-treat ( ITT ) was not performed, the Pembrolizumab treatment effect increased with PD-L1 enrichment.

Overall survival follow-up is ongoing.

Grade 3-5 treatment-related adverse effects rates were 68.1% with Pembrolizumab + chemotherapy ( 2 deaths ) vs 66.9% with chemotherapy ( 0 deaths ); rates of grade 3-4 immune-mediated adverse effects and infusion reactions were 5.5% vs 0%.

In conclusion, Pembrolizumab combined with several chemotherapy partners have shown a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy alone in patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer whose tumors expressed PD-L1 ( CPS greater than or equal to 10 ).
Pembrolizumab + chemotherapy was generally well tolerated, with no new safety concerns. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020

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