Randomized phase 2 trial of patritumab (P) or placebo (PBO) + cetuximab (C) + cisplatin (CIS) or carboplatin (CAR) for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

Authors

null

Kevin J. Harrington

Royal Marsden Hospital/Institute of Cancer Research, London, United Kingdom

Kevin J. Harrington , Martin David Forster , Christophe Le Tourneau , Jose Ariza , Shuquan Chen , Jonathan Greenberg , Kenji Hirotani , Eva Remenar

Organizations

Royal Marsden Hospital/Institute of Cancer Research, London, United Kingdom, University College London Hospitals/UCL Cancer Institute, London, United Kingdom, Institut Curie, Paris, France, UCLH - Cancer Clinical Trials Unit, London, United Kingdom, Daiichi Sankyo Inc., Basking Ridge, NJ, Daiichi Sankyo, Inc., Basking Ridge, NJ, Daiichi Sankyo Co., Ltd., Tokyo, Japan, National Institute of Oncology, Budapest, Hungary

Research Funding

Pharmaceutical/Biotech Company

Background: P, a fully human monoclonal antibody can block HER3 activation. HER3 activation is a resistance mechanism to C, induced by the ligand heregulin (HRG). This randomized phase 2 study in Europe evaluated first-line C + CIS or CAR + P or PBO for R/M SCCHN. Methods: Patients (pts) age ≥18 y with confirmed R/M SCCHN, stratified by HRG high vs low expression (via RT-PCR from tumor RNA) and human papilloma virus (HPV)+ vs HPV-, received IV P (18 mg/kg loading dose [LD]; 9 mg/kg maintenance dose [MD] every 3 weeks [q3w]) or PBO, and C (400 mg/m2 LD; 250 mg/m2 MD weekly) + ≤6 cycles of CIS (100 mg/m2 q3w) or CAR (AUC of 5). Co-primary endpoints were progression-free survival (PFS) in the intent-to-treat (ITT) and HRG high arms. Results: In all, 87 pts (44 P, 43 PBO; median age 59 y; 83% male) were treated; a median 6 (1-20) P cycles were completed. Pts received CAR (70%) or CIS (34%) (median 5 [2-6] CAR and 5 [1-6] CIS cycles) in the P arm and CAR (7%) or CIS (20%) (median 5 [1–6] cycles each) in the PBO arm. Discontinuations due to adverse events (AEs) were higher with P (16%) vs PBO (5%). Treatment-emergent AEs grade ≥3 were more frequent with P (84%) vs PBO (58%) (most frequent: acneiform dermatitis [14% vs 7%] and rash [14% vs 0%]). Serious AEs occurred in 43% (41% grade ≥3) (P) and 37% (33% grade ≥3) (PBO) of pts. In P and PBO arms, PFS and objective response rates (ORR; complete + partial response) in ITT, HRG-high (Table), HRG low (difference in PFS: HR 1.2, 95% CI 0.6–2.6, and ORR: 11.1%, 95% CI -15.8–36.0) and HPV- (difference in PFS: HR 1.5, 95% CI 0.9–2.7, and ORR: 4.7%, 95% CI -16.6–25.3) arms were similar (HPV+ arm was too small [n = 16] to draw meaningful results). Conclusions: P + C + CIS or CAR was not more effective than C + CIS or CAR. Clinical trial information: NCT02633800

PFS, mo,
median (95% CI)
P
PFS, mo,
median (95% CI)
PBO
PFS difference,
HR (95% CI)
P vs PBO
ORR,
% (95% CI)
P
ORR,
% (95% CI)
PBO
ORR difference,
% (95% CI)
P vs PBO
ITT
(N = 87)
n = 44
5.6
(4.1–6.5)
n = 43
5.5
(4.2–6.5)
1.11
(0.7–1.9)
P= 0.70
n = 16/44
36.4
(22.8–52.3)
n = 12/43
27.9
(15.8–43.9)
8.5
(-10.9–26.8)
HRG high (n = 51)n = 26
5.6
(4.1–7.1)
n = 25
5.6
(3.1–8.3)
1.12
(0.6–2.3)
P= 0.75
n = 11/26
42.3
(24.0–62.8)
n = 9/25
36.0
(18.7–57.4)
6.3
(-19.1–30.4)

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Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Head and Neck Cancer

Track

Head and Neck Cancer

Sub Track

Biologic Correlates

Clinical Trial Registration Number

NCT02633800

Citation

J Clin Oncol 36, 2018 (suppl; abstr 6045)

DOI

10.1200/JCO.2018.36.15_suppl.6045

Abstract #

6045

Poster Bd #

33

Abstract Disclosures