135MO - HRQoL with neoadjuvant pembrolizumab + chemotherapy vs placebo + chemotherapy, followed by adjuvant pembrolizumab vs placebo for early-stage TNBC: Results from KEYNOTE-522

Background

In the phase III KEYNOTE-522 study (NCT03036488), neoadjuvant (neoadj) pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo followed by adjuvant (adj) pembro vs pbo in patients (pts) with early-stage TNBC showed a statistically significant improvement in pCR (ypT0/Tis ypN0) and EFS (dual primary endpoints). We present PRO endpoint results from KEYNOTE-522.

Methods

Pts with previously untreated, nonmetastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to neoadj pembro 200 mg Q3W or pbo, both given with 4 cycles of paclitaxel + carboplatin then 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, pts received adj pembro or pbo for up to 9 cycles. PROs measured with EORTC QLQ-30 and QLQ-BR23 were prespecified secondary objectives, and with EQ-5D VAS were exploratory objectives. PROs were assessed during the neoadj and adj treatment phases and analyzed for pts who received at least 1 study treatment and completed ≥1 PRO assessment within the neoadj and adj treatment phases. Between-group differences in LS mean change from baseline to the latest time point with ≥60%/80% completion/compliance were assessed using a longitudinal model (no alpha assigned). A threshold of 10 points has been published as a meaningful change.

Results

PRO analyses for QLQ-C30 included 1145 pts in the neoadj phase (pembro + chemo; n = 762; pbo + chemo, n = 383) and 847 in the adj phase (n = 539; n = 308). Completion/compliance rates at wk 21 in neoadj phase and wk 24 in adj phase were ≥80% in both pembro and pbo groups. There were no meaningful differences between treatment group in PRO results (Table). Table: 135MO

Between-group difference in LS mean change from baseline to Wk 21 (Neoadj) or Wk 24 (Adj) in PRO endpoints in all pts with TNBC

^aPRO score range: 0–100.^bQLQ-C30 (pembro + chemo, n = 762; pbo + chemo, n = 383); QLQ-BR23 (n = 759; n = 382); EQ-5D VAS (n = 762; n = 384).^cQLQ-C30 (n = 539; n = 308); QLQ-BR23 (n = 538; n = 306); EQ-5D VAS (n = 540; n = 310).

Conclusions

Neoadj pembro + chemo followed by adj pembro did not have a negative meaningful impact on HRQoL vs pbo control in pts with previously untreated early-stage TNBC, reinforcing the clinical benefit seen with this regimen.

Clinical trial identification

NCT03036488.

Editorial acknowledgement

Writing support was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA), funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

R.A. Dent: Financial Interests, Personal, Other, Advisory/Consultancy: AstraZeneca, Novartis; Financial Interests, Personal, Other, Advisory/Consultancy, Travel/Accommodation/Expenses: Eisai, Merck, Pfizer, Roche. J. Cortés: Financial Interests, Personal, Advisory Role, Consultancy; Travel/Accomodation/Expenses; Honoraria: Roche; Financial Interests, Institutional, Research Grant, Research Grant Funding: Roche; Financial Interests, Personal, Other, Travel/Accomodation/Expenses; Honoraria: Novartis; Financial Interests, Personal, Advisory Role, Consultancy; Honoraria: Celgene, Lilly, Merck; Financial Interests, Personal and Institutional, Other, Travel/Accomodation/Expenses; Honoraria, Research Grant Funding: Eisai, Pfizer; Financial Interests, Personal, Other, Honoraria: Samsung Bioepis; Financial Interests, Institutional, Research Grant: Merk; Financial Interests, Personal, Advisory Role, Consultancy: Cellestia, Biothera, Merus, Seattle Genetics, Erytech, Athenex, Polyphor, Servier, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Research Grant Funding: AstraZeneca; Financial Interests, Personal, Advisory Role, Consultancy; Travel/Accomodation/Expenses: Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Funding: Ariad, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Guardian Health, Piqur, Puma C, Queen Mary University of London, Seagen; Financial Interests, Personal, Stocks/Shares: MedSIR. L. Pusztai: Financial Interests, Personal, Advisory Role, Consultancy; Travel/Accomodation/Expenses: Merck, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Research Grant, Funding: Merck, AstraZeneca, Seattle Genetics; Financial Interests, Personal, Advisory Role, Consultancy; Travel/Accomodation/Expenses; Honoraria: Novartis, Genentech, Eisai, Pieris, Immunomedics, Almac, Syndax. H.L. McArthur: Financial Interests, Personal, Invited Speaker, Consultancy; Travel/Accomodation/Expenses: Merck, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Funding: Merck, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consultancy; Travel/Accomodation/Expenses: Spectrum Pharm, Lilly, Amgen, Immunomedics, Pfizer, Genentech, AstraZeneca; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Puma Biotechnology. S. Kuemmel: Financial Interests, Personal, Other, Consulting Fees: Roche, Genomic Health, Novartis, Amgen, Celgene, Daiichi Sankyo, AstraZeneca, Somatex, Merck, Pfizer; PFM Medical, Lilly, Sonoscape; Financial Interests, Personal, Ownership Interest: WSG Study Group; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Roche, Daiichi, Sankyo, Sonoscape. J. Bergh: Financial Interests, Institutional, Research Grant, Funding: Amgen, AstraZeneca, Bayer, Merck, Roche, Pfizer, Sanofi Aventis; Financial Interests, Institutional, Other, Honoraria from UpToDate: Asklepios Medicin Hb. C. Denkert: Financial Interests, Personal, Other, Honoraria: Teva, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Consultancy, Honoraria: Amgen; Financial Interests, Personal, Advisory Role, Consultancy: MSD, Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Sividon (Myriad); Financial Interests, Personal, Licensing Fees, Royalties: VmScope. Y.H. Park: Financial Interests, Institutional, Advisory Board: AstraZeneca, Pfizer, Eisai, Roche, Novartis; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Pfizer, Eisai, Roche, Novartis; Financial Interests, Institutional, Funding: AstraZeneca, Merck, Pfizer, Novartis, Alteogen, Roche. R. Hui: Financial Interests, Personal, Other, Advisory Board/Personal fees for advisory boards: MSD, AstraZeneca, BMS, Eli Lilly, Merck, Novartis, Oncosec, Pfizer, Roche, Seagen; Financial Interests, Personal, Other, Speaker honoraria: MSD, Novartis, Roche; Financial Interests, Institutional, Funding, Study funding: MSD, AstraZeneca, BMS, Corvus, Eli Lilly, Janssen, Novartis, Olema, Oncosec, Roche, Seagen. N. Harbeck: Financial Interests, Personal, Stocks/Shares, Ownership Interest: West German Study Group; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Zodiac Pharma; Financial Interests, Personal, Other, Advisory Role/Consultancy: Agendia, AstraZeneca, Celgene, Daiichi Sankyo, Lilly, Merck, Novartis, Odonate Therapeutics, Pfizer, Pierre Fabre, Roche/Genentech, Sandoz, Seattle Genetics, West German Study Group (I); Financial Interests, Institutional, Funding: Lilly, Merck, Novartis, Pfizer, Roche/Genentech. M. Takahashi: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Pfizer, Lilly, Eisai; Financial Interests, Institutional, Research Grant, Research funding: Eisai, Taiho, Kyowa-Hakko Kirin, Nippon Kayaku. M. Untch: Financial Interests, Personal, Other, Consulting Fees: Amgen, Pfizer, Mundipharma, Roche, Lilly, Celgene, MSD, Novartis, AbbVie, Daiichi Sankyo, Pierre Fabre, Mylan, Myriad, GSK, AstraZeneca, Gilead, Molecular Health; Financial Interests, Personal, Other, Contracted research: German Breast Group, BMS, MSD, Polyphor, Daiichi Sanyko, Merck. P.A. Fasching: Financial Interests, Personal, Other, Consulting Fees: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, MSD, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia; Financial Interests, Personal, Other, Fees for Non-CME services received directly from commercial interest or their agents: Novartis, Daiichi Sankyo, Lilly, Seagen. Research grant; Author; Biontech, Cepheid. F. Cardoso: Financial Interests, Personal, Other, Advisory Role/Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanof. A. Haiderali, L. Jia, A.M. Nguyen, W. Pan: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J. O'Shaughnessy: Financial Interests, Personal, Other, Consulting fees: AbbVie, Agendia, Amgen, Aptitude Health, AstraZeneca, Bayer, BMS, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myri. P. Schmid: Financial Interests, Personal, Other, Consultancy, Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, Celgene; Financial Interests, Institutional, Other, Research Grant/Funding: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation; Financial Interests, Personal, Other, Spouse is an employee: Roche.