Abstract 798P
Background
No standard second-line treatment is available for AEC after failure to platinum-based chemotherapy in Europe. P conferred a 57% objective response rate (ORR) in patients (pts) with mismatch repair-deficient (MMRd) AEC. However, MMR-proficient (MMRp) AEC pts experience less benefit from immunotherapy. Our hypothesis was that P with an inducer of immunogenic cell death such as D could improve clinical responses in all AEC subtypes.
Methods
This was an investigator-initiated, single-arm, multicentre, phase II study in pts with AEC who have received one prior line of platinum-based chemotherapy (NCT03276013). Pts received D 60 mg/m2 i.v. every 3 weeks for up 9 cycles + P 200 mg up 36 cycles, or until progression or toxicity. Primary endpoint was progression-free survival (PFS) rate at 6 months (m). Secondary endpoints included ORR, duration of response (DOR), PFS, overall survival (OS) and safety.
Results
A total of 48 pts were enrolled. Median age was 66 years (range, 37-80). Most common EC histological types: endometrioid (64.6%), serous (20.8%), carcinosarcoma (8.3%), mixed carcinoma (4.2%) and others (2.1%). Median follow-up was 19.1 m with a median PFS of 6.2 m (95%CI, 4.8 – 8.7). The 6-m PFS was 53% (95%CI, 40.4% – 69.5%), which was a statistically significant improvement compared to the pre-defined 24% based on historical data (p< 0.001). The 6-m PFS rate was higher for patients with endometroid vs patients with non-endometroid histological subtype (63% vs 35%). The ORR was 31.3% (12.5% complete responses). Median OS and DOR were 16.3 (95%CI, 11.8 – NR) and 8.2 m (95%CI, 6.2 – NR), respectively. Serious treatment-related adverse events (TRAE) occurred in 7 (15%) patients, and one treatment-related death due to intracranial haemorrhage was reported. The most common grade ≥3 TRAE were neutropenia (25%) and lymphocyte count decreased (8.3%).
Conclusions
The combination of pembrolizumab and doxorubicin showed promising antitumor activity with a manageable safety profile in women with AEC after failure to platinum therapy. Translational analyses are ongoing to correlate biomarkers with outcomes.
Clinical trial identification
EudraCT 2017-002824-26; Release date: 03 July 2017.
Editorial acknowledgement
Legal entity responsible for the study
Vall d'Hebron Institute of Oncology (VHIO).
Funding
MSD.
Disclosure
L. Fariñas-Madrid: Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GSK. M.J. Rubio: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: PharmaMar. A. Redondo: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AtraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: PharmaMar; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Pharmamar; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Tesaro (GSK). G. Villacampa Javierre: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD. A. Yubero Esteban: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: PharmaMar. I. Romero: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: PharmaMar; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: PharmaMar; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology. M. Gil-Martin: Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: PharmaMar; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: PharmaMar; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: MSD. J. Garcia-Donas: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Principal Investigator: Bayer; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Research Grant: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology. A. González-Martín: Financial Interests, Personal, Advisory Role: Alkermes; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: GenMab; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Inmunogen; Financial Interests, Personal, Advisory Role: Oncoinvent; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Sotio; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: PharmaMar; Financial Interests, Personal, Leadership Role: GEICO; Financial Interests, Personal, Leadership Role: ENGOT. A. Gallego Martinez: Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: PharmaMar; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Pierre-Fabre. B. Pardo Búrdalo: Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel/Accommodations/Expenses: GSK; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology. M.L. Sanchez Lorenzo: Financial Interests, Personal, Other, Congress inscription: AstraZeneca; Financial Interests, Personal, Other, Educational activities: Clovis Oncology; Financial Interests, Personal, Other, Educational activities: Guardant Health; Financial Interests, Personal, Other, Congress inscription: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Other, Congress inscription: Pfizer; Financial Interests, Personal, Other, Congress inscription: PharmaMar; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Congress inscription: Roche; Financial Interests, Personal, Invited Speaker: GSK. J.M. Piulats: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Research Grant: BeiGene; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: VCN; Financial Interests, Personal, Advisory Role: Immunocore. A. Oaknin: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Inmunogen; Financial Interests, Personal, Advisory Board: Genmab; Financial Interests, Personal, Advisory Board: Mersana Therapeutic; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Deciphera Pharmaceutical; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Abbvie Deutschland; Financial Interests, Institutional, Sponsor/Funding: Ability Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Advaxis Inc.; Financial Interests, Institutional, Sponsor/Funding: Aeterna Zentaris; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: Aprea Therapeutics AB; Financial Interests, Institutional, Sponsor/Funding: Clovis Oncology; Financial Interests, Institutional, Sponsor/Funding: Eisai; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Regeneron Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: ImmunoGen; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Sharp & Dohme; Financial Interests, Institutional, Sponsor/Funding: Millenium Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Tesaro (GSK); Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Bristol Meyers Squibb. All other authors have declared no conflicts of interest.