Startseite Kongressberichte 2017 ESMO 2017 Congress Head & Neck Cancer Highlights Abstract LBA45_PR ‘Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 3 KEYNOTE-040 trial’

KEYNOTE-040 evaluates pembrolizumab in head and neck cancer

ESMO PRESS RELEASE/LUGANO-MADRID, 11 September, 2017 – Immunotherapy with the checkpoint inhibitor pembrolizumab may be a better option than standard treatments for patients whose head and neck cancer has spread, or recurred after an initial round of chemotherapy, according to results of the Keynote-040 trial presented at the ESMO 2017 Congress in Madrid. (1)

Although the 19% improvement in overall survival among patients treated with pembrolizumab did not meet the prespecified difference for statistical significance, it was nevertheless a clinically meaningful difference for this population who only lived seven to eight months, on average, after initiating treatment, said lead investigator Dr. Ezra Cohen, from the University of California, San Diego Moores Cancer Center, in La Jolla, California. 

“Even though the study did not meet its primary endpoint, I still think it is a positive trial,” he said. “It reinforces that pembrolizumab should continue to be offered as an important option for all patients with this devastating disease.” 

The KEYNOTE-040 trial was a global, open-label, phase 3 study which included patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after a platinum-based chemotherapy.

Patients were randomised to receive either pembrolizumab (n=247) or standard of care (SOC) treatment (n=248), which was the investigator’s choice of either methotrexate, docetaxel, or cetuximab.

Median overall survival (OS) was only marginally higher in the pembrolizumab compared to standard treatment arm (8.4 versus 7.1 months, hazard ratio [HR] 0.81 95% CI 0.66-0.99, P= .0204), however for a subset of patients who had PD-L1-expressing tumours, pembrolizumab was associated with dramatic and significantly improved outcomes.

Specifically, among patients with PD-L1-expression in more than 1% of all cells in their tumour, median OS was 8.7 months with pembrolizumab versus 7.1 months with standard treatments (HR 0.75; 95% CI 0.59-0.95, P=.0078), and among patients with PD-L1-expression in more than 50% of their cancer cells, median OS was 11.6 versus 7.9 months respectively (HR 0.54; 95% CI 0.35-0.82, P=.0017).

Compared to the other treatments, pembrolizumab measured up well in terms of side-effects.

“In almost every category it had a better side-effect profile, meaning a lower incidence of toxicity, versus standard treatments,” said Cohen. “The exception is hypothrodism, which occurred in 13% of those treated with pembro versus only 1% of those given other treatments.”

Overall, Cohen said the KEYNOTE-040 trial reinforces what is already known about anti-PD therapy in head and neck cancer. “From a clinician’s perspective I would feel the same in any country. This is a meaningful therapy that improves survival.”

Asked to comment for ESMO, Dr. Amanda Psyrri, from the University of Athens Medical School, and Attikon University Hospital in Athens said: “Keynote-040 did not reach its primary endpoint of overall survival; however, pembrolizumab was superior to investigator’s choice in terms of toxicity, an important consideration in treatment decisions for these poor-prognosis patients with recurrent/metastatic platinum-refractory HNSCC. As the authors point out, subsequent immunotherapy in the SOC arm may have confounded OS analysis. The magnitude of treatment effect was greater in patients with PD-L1 combined positive score (CPS) ≥ 1%, especially those with CPS ≥50%,suggesting that pembrolizumab may represent the preferable treatment option for this subset of patients.”


Notes to Editors

Please make sure to use the official name of the meeting in your reports: ESMO 2017 Congress


1 Abstract LBA45_PR ‘Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): Phase 3 KEYNOTE-040 trial’ has been presented by Dr. Cohen during Proffered Paper Session 'Head and neck cancer' on Monday, 11 September 2017, 15:00 to 16:20 (CEST) in Granada Auditorium.

Background: Pembro showed antitumor activity and manageable toxicity in R/M HNSCC in an extended phase 1b study. KEYNOTE-040 (NCT02252042) was a global, open-label, phase 3 study of pembro vs SOC for R/M HNSCC.

Methods: Eligible pts with SCC of the oral cavity, oropharynx, hypopharynx, or larynx who had recurrence or PD after a platinum-containing regimen were randomized 1:1 to pembro 200 mg Q3W for 24 mo or investigator choice of standard doses of methotrexate (M), docetaxel (D), or cetuximab (C). Randomization was stratified by ECOG PS (0 vs 1), HPV status (p16 positive vs negative), and PD-L1 tumor proportion score (TPS) (≥50% vs <50%). Treatment was given until confirmed PD or intolerable toxicity. Primary end point was OS in the ITT population. Key secondary end points were OS in pts with PD-L1 combined positive score (CPS) ≥1% and PFS and ORR in the ITT and CPS ≥1% populations. Prespecified efficacy boundary for OS in the ITT population was one-sided P = .0175.

Results: 495 pts enrolled: 247 were assigned to pembro, 248 to SOC (65 M, 110 D, 73 C). After median follow-up of 7.3 mo, 8.9% of pts remained on pembro, 0.9% on SOC. Pembro prolonged OS in the ITT population, but the difference did not achieve statistical significance (HR 0.81, one-sided P = .0204; Table). There was no difference in PFS (Table). ORR was higher with pembro (Table). Pembro outcomes were improved in pts with PD-L1–expressing tumors (Table). 12.5% of pts in the SOC arm received subsequent immunotherapy, potentially impacting OS. Grade 3-5 drug-related AE incidence was 13.4% with pembro and 36.3% with SOC; 1.6% and 0.9%, respectively, died of drug-related AEs.



PD-L1 CPS ≥1%

PD-L1 TPS ≥50%


N = 247

N = 248

n = 196

n = 191


n = 64

n = 65


(95% CI), mo







HRa (95% CI)

0.81 (0.66-0.99)

0.75 (0.59-0.95)

0.54 (0.35-0.82)






(95% CI), mo







HRa (95% CI)

0.95 (0.79-1.16)

0.89 (0.72-1.11)

0.58 (0.39-0.87)





ORR,c %











aOne-sided P value stratified by the randomization stratification factors.

bNominal only.

cAssessed per RECIST v1.1 by blinded, independent central review.



Conclusions: Pembro provided an 19% reduction in the risk of death over SOC in pts with R/M HNSCC, although the prespecified efficacy boundary was not reached; subsequent immunotherapy in the SOC arm may have confounded OS analysis. Greater differences in OS, PFS, and ORR favoring pembro were seen in patients with PD-L1 expressing tumors.

Clinical trial identification: number NCT02252042, originally posted Sep 25, 2014; EudraCT number 2014-001749-26, originally issued 1-Aug-2014

Legal entity responsible for the study: Merck & Co., Inc., Kenilworth, NJ USA

Funding: Merck & Co., Inc., Kenilworth, NJ, USA