Choosing the Right Treatment Option for the Right R/M HNSCC Patient: Should We Adhere to PFE for First-Line Therapy?

Katharina Lübbers,Andreas Dietz,Susanne Wiegand,Theresa Wald,Veit Zebralla,Gunnar Wichmann,Mykola Pavlychenko

doi:10.3389/fonc.2021.715297

Abstract

BackgroundThe landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE).MethodsFor this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival.ResultsSubgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen.ConclusionThis retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making.

Highlights

Squamous cell carcinoma of the head and neck (HNSCC) is an entity with growing importance, in clinical and in research settings
Patients receiving surgery followed by postoperative radio-chemotherapy (PORCT; n = 52) had a prolonged median time from curative treatment to 1L-ChT of 30.6 months (95%CI: 21.5–40.2) compared to 10.4 months of patients with other types of curative treatment
As the median time from curative treatment with surgery followed by cisplatin-based PORCT to 1L-ChT (n = 52) was 30.6 months (95%CI: 21.5–40.2) and substantially longer (P = 0.005) compared to 10.6 months (95%CI: 5.0–16.3) of patients without prior treatment or other types of prior curative treatment, and these cisplatin-pretreated R/M HNSCC patients had the highest benefit from PFE, treatment escalation in presence of risk factors in the curative setting improves outcome and does not reduce OS1L-ChT if PFE is used

Summary

Introduction

Squamous cell carcinoma of the head and neck (HNSCC) is an entity with growing importance, in clinical and in research settings. According to the NCCN Guidelines for Head and Neck Cancer (2018) [2], curative therapy is considered appropriate until UICC IVB, whereas detection of distant metastasis (M1 defining stage IVC) means loss of curative treatment options advising switch to systemic treatment and palliative care (with the only exception of resectable solitary M1). While there are certain therapy algorithms for HNSCC in curable stages, only a few approved options for first-line chemotherapy and other systemic first-line therapies (altogether summarized under the abbreviation 1L-ChT) are available in case of R/M HNSCC following the NCCN guidelines from 2018. Since publication of the landmark EXTREME trial [3], treatment with up to six cycles of cisplatin, 5-fluorouracil and cetuximab (PFE), became standard 1L-ChT in R/M HNSCC. The landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE)

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Results

Discussion

Conclusion