Startseite Kongressberichte & Archiv ESMO 2017 Congress Head & Neck Cancer Highlights 1. First line Cetuximab and Cisplatin with or without Paclitaxel/2. The observational ENCORE study: Cetuximab + platinum-based therapy

LBA47 - First line Cetuximab and Cisplatin with or without Paclitaxel in recurrent/metastatic head and neck cancer: a randomized phase IIb trial

P. Bossi et al.

Background

Cisplatin (Cis), continuous infusion 5FU and Cetuximab (Cet) (EXTREME) first-line treatment extends overall survival (OS) over Cis and 5FU of recurrent/metastatic squamous cell head and neck cancer (RM SCCHN) patients. In EXTREME, Cet has been added to a 2-drug combination, which has never shown superiority over any single drug. In this scenario, we are left with an open question about the significance of adding 1 or 2 drugs to biotherapy. In addition, a significant number of pts are excluded from EXTREME for the high incidence of ≥ G3 adverse events (AEs) (>80%), most of them attributable to 5FU. Paclitaxel (P) is active and safe, both alone and with Cis. We conducted a phase IIb trial comparing a 2-drug Cet-Cis regimen with a 3-drug combination (substituting 5FU with P) in terms of progression-free survival (PFS) and tolerability.

Methods

Eligible pts had confirmed untreated R/M SCCHN. Pts were randomized to a 3 vs. a 2-drug combination (Cet + Cis w/o P) with maintenance Cet after 6 cycles. Primary endpoint was PFS; secondary end-points were overall survival (OS), response rate (RR) and toxicity. We assumed a non-inferiority margin of 1.40 as compatible with efficacy.

Results

200 pts were randomized and 191 evaluable. Pt characteristics were balanced in the 2 arms. Inferiority hypothesis was rejected (upper limit of one-sided 90% CI of PFS hazard ratio<1.4). Median PFS was 6 and 7 mos (95% CI: 5-7 and 6-8 mos) in the 2 vs. 3-drug arms, respectively (p=NS), median OS was 13 and 11 mos (95% CI: 10-16 and 9-14 mos) (p=NS), and RR was 42% vs 52% (p=NS). Grade ≥ 3 AEs were 76% and 73% for the 2 vs 3-drug regimen, respectively. Skin rash and electrolyte alterations were mainly reported in the 2-drug arm, while haematological toxicities and infections in the 3-drug arm. No toxic death and sepsis were reported and cardiac events were negligible (1%).

Conclusions

A 2-drug Cet and Cis regimen proved to be non-inferior in PFS to a 3-drug combination with Cet, Cis and P. The median OS of both regimens is comparable with the 10.1 mos in EXTREME, while life-threatening toxicity rate appeared reduced. These regimens warrant further investigation as a backbone to immunotherapeutic agents.

Clinical trial identification

EudraCT: 2011-002564-24

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori Milano

Funding

Merck Serono

Disclosure

All authors have declared no conflicts of interest.

 

1068P - The observational ENCORE study: Cetuximab + platinum-based therapy for first-line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head & neck

Le Tourneau et al.

Background

The randomized, phase 3 EXTREME study established cetuximab + platinum + 5-flurouracil (5-FU) followed by cetuximab maintenance until progressive disease (PD) as the first regimen to yield survival benefits in the 1L management of patients with R/M SCCHN. In EXTREME, the addition of cetuximab increased the overall response rate from 20% to 36%, and extended progression-free survival from 3.3 to 5.6 months and overall survival from 7.4 to 10.1 months. ENCORE is a multinational, non-interventional, prospective, open-label study, seeking to determine how treatment decisions are made, planned and executed by oncologists treating patients with 1L therapy for R/M SCCHN in the real world.

Methods

ENCORE prospectively enrolled 219 patients with R/M SCCHN from Algeria, France, Italy, Portugal and Russia. The recommended treatment for these patients is cetuximab + PBT for up to 6 cycles followed by cetuximab maintenance until PD. Patient characteristics, drugs and schedule were recorded; as the study is still ongoing, safety and efficacy will not be reported here.

Results

ENCORE patients and the EXTREME patients who received cetuximab + platinum + 5-FU had similar performance status (PS: 13.7 and 12% with PS ≥ 2, respectively), but dissimilar median age (64 and 56 years, respectively). In ENCORE, 94.1% of patients had a planned treatment of cetuximab + PBT with cetuximab maintenance until PD. The remaining 13 (5.9%) had a fixed treatment duration of 4 to 24 weeks. 37.9% of treatment plans used cisplatin, 61.6% included carboplatin and 3.2% used a taxane. Also, only 53.4% of plans included 5-FU. When developing the treatment plan, 72.1% of all patients were discussed within the context of a multidisciplinary team (MDT). Most plans had the goal of palliative care, and 80% were formulated without a p16 or human papillomavirus status test. Updated data will be presented at congress.

Conclusions

The ENCORE study shows that a real-world R/M SCCHN patient population treated with the EXTREME regimen has diverse characteristics and is treated per current recommendations (e.g. in an MDT setting, with cetuximab until PD).

Clinical trial identification

EMR 62202-566

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany

Funding

Merck KGaA, Darmstadt, Germany

Disclosure

C. Le Tourneau: Consultancy: Novartis, MSD, Bristol-Myers Squibb, AstraZeneca; Honoraria: Merck Serono J. Schulten: Full Time Employee: Merck KGaA. D. Messinger: Employee/Consultancy: Employee of Prometris GmbH, which has a contract with Merck KGaA regarding statistical consultancy. All other authors have declared no conflicts of interest.