912P - Results of a randomized phase II study comparing pembrolizumab with methotrexate in elderly, frail or cisplatin-ineligible patients with relapsed or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) (ELDORANDO-AIO-KHT-0115)

Background

Platinum-based chemotherapy is a standard of care (SOC) in RM-SCCHN. A substantial number of patients (pts.) are not eligible for such treatment and a SOC is not defined in these patient population. We therefore tested whether pembrolizumab (PEM) is superior to methotrexate (MTX) in pts. ineligible for platinum-based therapy.

Methods

Pts. with previously untreated, measurable (RECIST 1.1) RM-SCCHN with ECOG 0-2, >18 years of age and adequate organ function (except GFR) were eligible. Cisplatin-ineligibility was determined by ECOG 2 and/or calculated GFR <60 ml/min. Pts. were randomized to PEM 200 mg q3w i.v. or MTX 40 mg/m2 weekly i.v. until progression or intolerance. Primary endpoint was 1 year overall survival (OS) rate (1YOS). The trial was terminated early after 47 of 100 pts due to poor accrual and change in therapeutic landscape. Statistical analyses consisted of chi-square, log-rank or cox proportional hazard, where appropriate.

Results

23 and 24 pts. were randomized to PEM and MTX, respectively. Mean age was 71.4 (43-90) years, 34 (72.3%) were male, 41 (87.2%) pts. had ECOG=2 and 12 (25.5%) pts. had an HN-CCI of at least 2. Median follow-up was 5 mo. (IQR 1.0-13.0). No major difference for PFS or OS were detected (shown in table). Subsequent therapies received 12 pts (25.5%). Any and grade 3-5 TRAE for PEM/MTX occurred in 9 (40.9%)/17 (70.8%) and 2 (9.1%)/7 (29.2%) pts, respectively. SAEs were reported in 12 (54.5%) and 16 (66.7%) for PEM and MTX, respectively. Table: 912P

Efficacy parameter for 1st line pembrolizumab vs. methotrexate in platin-ineligible patients with RM-SCCHN

Conclusions

We did not detect large differences in ORR, PFS or OS between 1st line treatment with PEM or MTX in cisplatin-inelgibile RM-SCCHN. However, prognosis of cisplatin-ineligible pts. remained poor and safety parameter favored PEM. The study size was a major limitation. Additional studies are warranted to investigate the best therapeutic approach in these patients.

Clinical trial identification

NCT03193931.

Editorial acknowledgement

Legal entity responsible for the study

AIO Studien gGmbH.

Funding

MSD Sharp & Dohme.

Disclosure

V. Gruenwald: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Janssen-Cilag; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Nanobiotix; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: EUSAPharm; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Stocks/Shares: MSD; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Seattle Genetics; Financial Interests, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Invited Speaker: PharmaMar; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology. U. Graeven: Financial Interests, Personal, Invited Speaker: Daiicki Sankyo; Financial Interests, Personal, Invited Speaker: Boehringen Ingelheim; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Johnson&Johnson; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Travel: Merck; Financial Interests, Personal, Other, Travel: Amgen; Financial Interests, Personal, Other, Travel: Boehringen Ingelheim. P. Ivanyi: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: EUSAPharm; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Ipsen; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer. A. Dietz: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Research Grant: MSD; Non-Financial Interests, Personal, Leadership Role: DGHNO; Non-Financial Interests, Personal, Member: ESO. D. Hahn: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Board: Takeda. S. Hackenberg: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Nanobiotix; Financial Interests, Personal, Advisory Board: Karl Storz. S. Kasper: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Principal Investigator: Lilly; Financial Interests, Personal, Principal Investigator: Roche; Non-Financial Interests, Personal, Advisory Role: Amgen; Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: BMS; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: Merck; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Servier; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: DGHO. R. Fietkau: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: MSD. J. Moulin: Financial Interests, Personal, Other, Travel: Amgen. D. Pink: Financial Interests, Institutional, Invited Speaker: Blueprint; Financial Interests, Institutional, Invited Speaker: PharmaMar; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: EUSAPharm; Financial Interests, Institutional, Principal Investigator: Lilly; Financial Interests, Institutional, Other, Scientific lead of trial: Novartis; Financial Interests, Institutional, Principal Investigator: PharmaMar; Financial Interests, Institutional, Principal Investigator: Roche. K. Klinghammer: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Merck Sanofi; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal and Institutional, Principal Investigator: GSK; Non-Financial Interests, Personal and Institutional, Principal Investigator: Kura Onkologie; Non-Financial Interests, Personal, Member: DGHO; Non-Financial Interests, Personal, Member: DKG; Non-Financial Interests, Personal, Member: AIO; Non-Financial Interests, Personal, Member: ASCO. All other authors have declared no conflicts of interest.