New developments in the management of head and neck cancer – impact of pembrolizumab

Figures & data

Table 1 Main studies of immune checkpoint inhibitors in HNSCC

References	Phase/n	Treatment	Indication	Outcome
Seiwert et al^Citation44	Ib/n=60	Pembrolizumab 10 mg/kg every 2 weeks	Recurrent or metastatic PD-L1-positive HNSCC	RR =18%
Bauml et al^Citation46	II/n=174	Pembrolizumab 200 mg every 2 weeks	Platinum and cetuximab pretreated patients	RR =16% mDR: 8 months mOS: 8 months mPFS: 2 months
Chow et al^Citation45	Ib/n=131	Pembrolizumab 200 mg every 2 weeks	Recurrent or metastatic HNSCC, irrespective of PD-L1 status	RR =18% mDR: not reached 6-month OS: 59% 6-month PFS: 23%
Segal et al^Citation49	I/II/n=62	Durvalumab 10 mg/kg every 2 weeks	Recurrent and metastatic HNSCC	RR =11% 1-year OS: 62%
Ferris et al^Citation48	III/n=361	Nivolumab 3 mg/kg every 2 weeks	HNSCC progressing within 6 months after platinum-based chemotherapy	RR =13% mPFS: 2 months mOS: 7.5 months

Abbreviations: HNSCC, head and neck squamous cell carcinoma; mDR, median duration response; mOS, median overall survival; mPFS, median progression-free survival; PD-L1, programmed death-1 ligand; RR, response rate.

Table 2 Ongoing trials of pembrolizumab

	References	Phase/patients	Patients population	Agent	Endpoint
Adjuvant setting, surgically resectable HNSCC	NCT02641093	II/80	Resected HNSCC	Pembrolizumab + cisplatin and radiation	Toxicity and DFS
	NCT02296684	II/46	Surgically resectable, locally advanced HNSCC	Neoadjuvant pembrolizumab + surgery + adjuvant therapy (radiation therapy + cisplatin ± pembrolizumab)	Locoregional recurrences rates, distant failure rate
	NCT03057613	II/37	Resected, high-risk cutaneous HNSCC	Pembrolizumab + postoperative radiotherapy	Number of subjects with DLTs, PFS
	NCT02769520	II/45	Relapsed, locally recurrent HNSCC after salvage surgery	Pembrolizumab vs placebo	DFS
First-line locally advanced or metastatic setting	NCT02759575	I–II/47	Previously untreated, locally advanced laryngeal SCC	Pembrolizumab + cisplatin + radiation	Toxicity and laryngectomy-free survival in locally advanced laryngeal SCC
	NCT03114280	II/55	Untreated, unresectable, locally advanced HNSCC, stage III or IV without metastases	Induction therapy (docetaxel + cisplatin + 5-fluorouracil + pembrolizumab) followed by radiotherapy combined with carboplatin	PFS
	NCT02777385	II/44	Intermediate or high-risk, previously untreated, locally advanced HNSCC	Pembrolizumab started 3 weeks after completion of cisplatin + radiation vs pembrolizumab given 1 week prior to the start of cisplatin + radiation and given every 3 weeks	1-year PFS, 1-year failure rate, acute toxicity rate
	NCT02586207	I/39	Stage III–IVB HNSCC	Pembrolizumab + standard cisplatin-based definitive chemoradiotherapy	Monitor and grade AE
Cisplatin-ineligible patients	NCT03193931	II/100	Elderly, frail or cisplatin-ineligible patients with HNSCC	Pembrolizumab vs methotrexate	OS rate
	NCT02609503	II/29	Locally advanced HNSCC not eligible for cisplatin	Pembrolizumab + radiation	PFS
	NCT02707588	II/114	Locally advanced HNSCC not suitable for cisplatin-based chemotherapy	Pembrolizumab + radiotherapy vs cetuximab + radiotherapy	Locoregional control
Recurrent disease: pembrolizumab alone	NCT02252042	III/495	Recurrent HNSCC considered incurable by local or systemic disease and metastatic HNSCC considered incurable by local therapies	Pembrolizumab vs standard treatment (methotrexate, docetaxel or cetuximab)	OS for all participants
Recurrent disease: pembrolizumab combined to other therapies	NCT03082534	II/83	Recurrent/metastatic HNSCC	Pembrolizumab + cetuximab	ORR
	NCT02718820	I–II/22	Recurrent or metastatic HNSCC, progressing following receipt of cisplatin and/or carboplatin-based regimen independent of whether patient progressed during or after platinum-based therapy	Pembrolizumab + docetaxel	ORR
	NCT02358031	III/825	Recurrent or metastatic HNSCC considered incurable by local therapies	Pembrolizumab alone vs pembrolizumab + a platinum-based drug (cisplatin or carboplatin) + 5-fluorouracil vs cetuximab + a platinum-based drug (cisplatin or carboplatin) + 5-fluorouracil	PFS in PD-L1-positive expression, OS in PD-L1-positive expression, PFS in all participants, OS in all participants
	NCT02538510	I–II/50	Recurrent unresectable and/or metastatic HNSCC	Pembrolizumab + vorinostat	Incidence of toxicity
	NCT02289209	II/48	Locoregional inoperable recurrence or second primary HNSCC, in patients who have received only prior radiation treatment course with a curative intent	Re-irradiation + pembrolizumab	PFS
	NCT02626000	I/40	Recurrent or metastatic HNSCC >18 years, Eastern Cooperative Oncology Group Performance Status 0.1	Talimogene laherparepvec + pembrolizumab	Incidence of DLTs
Recurrent disease: pembrolizumab combined to other therapies after a treatment with checkpoint inhibitors	NCT03238638	II/30	HNSCC, with either prior response to anti-PD-1/PD-L1 and subsequent (acquired) resistance, or suboptimal benefit from prior PD-1/PD-L1 therapy	Pembrolizumab + epacadostat Acalabrutinib + pembrolizumab vs pembrolizumab	RR ORR in each arm
	NCT02454179	II/74	Advanced (recurrent, metastatic or unresectable) HNSCC that has either progressed during or after platinum-based chemotherapy administered for metastatic disease or has recurred during or within 6 months after the completion of platinum-based neoadjuvant or adjuvant therapy
	NCT03085719	II/26	Metastatic HNSCC considered incurable by local therapies, with progression or stabilization on prior PD-1 therapy	Pembrolizumab + high-dose radiation vs pembrolizumab + high-dose + low-dose radiation	ORR
Maintenance treatment	NCT02892201	II/24	HNSCC patients who have residual disease following definitive therapy with radiation (with or without systemic therapy)	Pembrolizumab	ORR
	NCT02841748	II/100	Stages IVA, IVB and select cases of stage III HNSCC at high risk of recurrence after completion of curative intent therapy	Pembrolizumab vs placebo	2-year PFS
	NCT03040999	III/780	Locally advanced HNSCC	Pembrolizumab + chemoradiation as maintenance therapy vs chemoradiation alone	EFS

Abbreviations: AE, adverse event; DLT, dose-limiting toxicity; EFS, event-free survival; HNSCC, head and neck squamous cell carcinoma; ORR, overall response rate; OS, overall survival; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; RR, response rate; SCC, squamous cell carcinoma; DFS, disease free survival.

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