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First-Line Pembrolizumab Plus Platinum-Based Chemotherapy ‘Standard Of Care’ For Advanced HNSCC

First-line pembrolizumab plus platinum-based chemotherapy improves recurrent and metastatic head and neck squamous cell carcinoma survival compared with the EXTREME regimen
02 Nov 2018
Anticancer Agents;  Head and Neck Cancers;  Immunotherapy

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Study findings demonstrate improved overall survival (OS) with pembrolizumab with or without platinum chemotherapy compared with a cetuximab-based regimen for treatment-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC). 

Barbara Burtness, from Yale School of Medicine and Yale Cancer Center in New Haven, Connecticut, USA, reported the findings of the KEYNOTE-048 trial at the ESMO 2018 Congress in Munich, Germany. 

“Data support pembrolizumab monotherapy as a new first-line standard-of-care for [recurrent/metastatic] HNSCC that expresses PD-L1”, she told delegates, and these results also support “pembrolizumab plus platinum-based chemotherapy as a new first-line standard of care for [recurrent/metastatic] HNSCC without the use of a biomarker.” 

The participants were randomly assigned to receive up to 35 cycles of pembrolizumab 200 mg every 3 weeks (n=300), or pembrolizumab plus six cycles of carboplatin or cisplatin given alongside fluorouracil (n=276), or the EXTREME regimen consisting of cetuximab plus carboplatin or cisplatin with fluorouracil (n=287). 

The primary endpoints of OS and progression-free survival (PFS)  were determined among the patients with a combined positive score (CPS) of at least 20% for the proportion of tumour cells, lymphocytes and macrophages expressing PD-L1, those with a CPS of at least 1%, and the full study population. 

Compared with EXTREME, pembrolizumab monotherapy in patients with a CPS of at least 20% was associated with a significant prolongation in OS, at a median of 14.9 versus 10.7 months and a hazard ratio (HR) for death of 0.61. 

There was also longer OS with pembrolizumab monotherapy in the CPS 1% or above population, at 12.3 versus 10.3 months and a HR of 0.78. However, there was no PFS benefit for pembrolizumab monotherapy compared with EXTREME for patients in either CPS subgroup. 

Furthermore, overall response rates were lower with pembrolizumab than EXTREME for both the CPS threshold of 20% (23.3 vs 36.1%) and 1% (19.1 vs 34.9%), although the corresponding durations of response in both groups were “substantially” longer with the PD-1 inhibitor (20.9 vs 4.2 and 20.9 vs 4.5 months, respectively). 

Barbara Burtness also reported the primary endpoint findings for pembrolizumab plus chemotherapy regimen versus EXTREME in the full study population; median OS was 13.0 months versus 10.7 months and a significant HR of 0.77 in favour of the pembrolizumab plus chemotherapy arm. 

PFS did not significantly differ between the pembrolizumab plus chemotherapy and EXTREME arms, with median durations of 4.9 and 5.1 months, respectively. The ORRs were also comparable, at 35.6% versus 36.3%, but again duration of response was longer in the PD-1 inhibitor arm, at 6.7 months versus 4.3 months with the cetuximab-based regimen. 

Barbara Burtness noted that pembrolizumab monotherapy was noninferior to EXTREME for OS in the overall study population and that further follow-up will look for superiority in OS with the PD-1 inhibitor, as well as examine for OS superiority for pembrolizumab plus chemotherapy in the CPS 20% or above group, and if so, in the CPS 1% and higher group. 

The KEYNOTE-048 investigator also reported safety findings for the regimens, highlighting that pembrolizumab monotherapy had a “favorable” profile compared with EXTREME, with lower rates of treatment-related adverse events and discontinuation, while the pembrolizumab plus chemotherapy had a “comparable” profile.


Burtness B, Harrington KJ, Greil R, et al. KEYNOTE-048: Phase 3 study of first-line pembrolizumab for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). ESMO Congress 2018; Munich, Germany: 19–23 October (LBA8_PR).

Watch the Expert Video Report: Immunotherapy for Head and Neck Cancer, by Marco Merlano

Last update: 02 Nov 2018

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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