HNSCC
KEYTRUDA monotherapy or plus chemotherapy versus EXTREMEa in M/uR HNSCC1,2
Indication1
KEYTRUDA, as monotherapy or in combination with platinum and 5-FU chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent HNSCC in adults whose tumours express PD-L1 with a CPS >=1.
KEYNOTE-048: a multicentre, randomised, open-label, active controlled phase 3 trial2,3
KEYNOTE-048 was a multicentre, randomised, open-label, active controlled study in patients with recurrent or metastatic HNSCC who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies.
Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible for the study. Patients were randomised 1:1:1 to KEYTRUDA 200 mg Q3W; KEYTRUDA 200 mg Q3W + carboplatin AUC 5 mg/m2 Q3W or cisplatin 100mg/m2 Q3W + 5-FU 1,000 mg/m2 per day for 4 consecutive days Q3W (maximum of 6 cycles of platinum and 5-FU); or cetuximab 400 mg/m2 load then 250 mg/m2 Q1W + carboplatin AUC 5 mg/m2 Q3W or cisplatin 100 mg/m2 Q3W + 5-FU 1,000 mg/m2 per day for 4 consecutive days Q3W (maximum of 6 cycles of platinum and 5-FU). Treatment with KEYTRUDA continued until RECIST 1.1 defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months.
Administration of KEYTRUDA was permitted beyond RECIST defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumour status was performed at week 9 and then every 6 weeks for the first year, followed by every 9 weeks through 24 months.2,3
a. Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU.2
b. The recommended dose of KEYTRUDA as monotherapy is either 200 mg every 3 weeks or 400 mg every 6 weeks administered an intravenous infusion over 30 minutes.1
c. Total population is not included in the Belgian label of KEYTRUDA; results are not shown in this document.1
5-FU = 5-fluorouracil; AUC = area under the curve; BICR = blinded independent central review; CPS = combined positive score; ECOG PS = Eastern Cooperative Oncology Group performance status; HNSCC = head and neck squamous cell carcinoma; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma; OR = objective response; OS = overall survival; p16 = tumour suppressor protein; PD-L1 = programmed death ligand 1; PFS = progression-free survival; Q1W = every week; Q3W = every 3 weeks; QoL = quality of life; RECIST 1.1 = Response Evaluation Criteria in Solid Tumors 1.1; SCC = squamous cell carcinoma.
KEYTRUDA monotherapy reduced the risk of death vs EXTREME1,3,a
PD-L1 CPS =1
26% reduction in the risk of death with KEYTRUDA monotherapy vs EXTREMEa for patients with PD-L1 expression CPS =11,3
PD-L1 CPS =20
42% reduction in the risk of death with KEYTRUDA monotherapy vs EXTREMEa for patients with PD-L1 expression CPS =201,3
Adapted from Supplement to Burtness et al., 2019.3
a.Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU.2
b.An event was death during the study.2
5-FU = 5-fluorouracil; CI = confidence interval; CPS = combined positive score; HR = Hazard ratio; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival.
- SmPC KEYTRUDA 03/2021 and KEYTRUDA (pembrolizumab).
- Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.
- Supplement to: Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.
KEYTRUDA in combination with platinum/5-FU reduced the risk of death vs EXTREME1,2a
35% reduction in the risk of death with KEYTRUDA + chemotherapy vs EXTREMEa for patients with PD-L1 expression CPS =11,2
Adapted from Burtness et al., 20192 and SmPC.1
a. Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU.2
b.An event was death during the study.2
5-FU = 5-fluorouracil; CI = confidence interval; CPS = combined positive score; HR = Hazard ratio; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival.
KEYTRUDA monotherapy and combination with platinum/5-FU extended duration of response vs EXTREME2,3,a
Median DoR was more than 5x longer with KEYTRUDA monotherapy compared with EXTREMEa for patients with PD-L1 expression CPS =12,3
ORR in patients with PD-L1 expression CPS =11,3
| Confirmed response, n (%) | KEYTRUDA n=257 | EXTREMEa n=255 |
|---|---|---|
| ORR | 49 (19) | 89 (35) |
| CR | 14 (5) | 7 (3) |
| PR | 35 (14) | 82 (32) |
| SD | 72 (28) | 84 (33) |
| PD | 100 (39) | 33 (13) |
| Non-CR/non-PDb | 11 (4) | 11 (4) |
| Not evaluable or assessedc | 25 (10) | 38 (15) |
Adapted from Supplement to Burtness et al., 2019.3
The ORR was 36% with KEYTRUDA (n=88/242; CR=16; PR=72) vs 36% with EXTREMEa (n=84/235; CR=7; PR=77)3
a.Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU.2
b.Non-CR/non-PD includes participants without disease measurable per RECIST, version 1.1, by blinded, independent central review at baseline who did not have complete response or progressive disease.3
c.Not evaluable or assessed includes participants who did not have a post-baseline imaging assessment evaluable for response or who did not have post-baseline imaging.3
5-FU = 5-fluorouracil; CI = confidence interval; CPS = combined positive score; CR = complete response; DoR = duration of response; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma; ORR = objective response rate; PD-L1 = programmed death ligand 1; PD = progressive disease; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumours; SD = stable disease.
- SmPC KEYTRUDA 03/2021 and KEYTRUDA (pembrolizumab).
- Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.
- Supplement to: Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.
KEYTRUDA monotherapy had a favourable safety profile vs EXTREME2,3,a
The discontinuation rate due to AEs was 12% with KEYTRUDA monotherapy vs 28% with EXTREME2,a
Adapted from Supplement to Burtness et al., 2019.3
Adapted from Burtness et al., 2019.3
a.Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU.2
5-FU = 5-fluorouracil; AE = adverse event; IQR = interquartile range; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma.
The safety profile of KEYTRUDA in combination with platinum/5-FU was comparable to EXTREME2,3,a
Patients treated with KEYTRUDA + chemotherapy had similar rates of AEs compared with patients treated with EXTREME2,a
Adapted from Supplement to Burtness et al., 2019.3
Adapted from Burtness et al., 2019.3
a.Patients receiving the EXTREME regimen were given cetuximab + carboplatin or cisplatin + 5-FU2
5-FU = 5-fluorouracil; AE = adverse event; M/uR HNSCC = metastatic or unresectable recurrent head and neck squamous cell carcinoma.
- SmPC KEYTRUDA 03/2021 and KEYTRUDA (pembrolizumab).
- Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.
- Supplement to: Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):19151928.