Jean-Pascal Machiels, Cliniques Universitaires St. Luc, Belgium:

LBA29
Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-head & neck 1, a phase III trial:

 

   

More Infos, ESMO Press Release & Abstract

LBA29
Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-head & neck 1, a phase III trial:

Second-line afatinib significantly improves progression-free survival in recurrent or metastatic head and neck cancer, phase III trial shows

Lugano/Madrid, 27 September 2014 -- The tyrosine kinase inhibitor afatinib significantly improved progression-free survival compared to methotrexate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy, the results of a phase III trial show.

Presented at the ESMO 2014 Congress in Madrid, the Lux-Head & Neck 1 trial showed that patients who received treatment with 40 mg/day oral afatinib had a 20% reduction in risk of progression or death compared to patients who received methotrexate, with a median progression-free survival of 2.6 months.

“The improvement in progression-free survival was associated with a significant delayed worsening of symptoms (such as pain, swallowing and global health status) versus chemotherapy. Patients treated with afatinib had less pain over time than patients treated with methotrexate. “These are important outcomes for patients with these conditions,” notes study author Dr Jean-Pascal Machiels, a medical oncologist at Institut Roi Albert II, Cliniques Universitaires St. Luc, in Brussels, Belgium.

Recurrent or metastatic squamous cell carcinoma of the head and neck often has a poor outcome, Machiels explains. “This is a poor prognosis population and a disease that does not get enough attention from the scientific community, because this group of patients often has severe co-morbidities and social problems such as alcoholism and tobacco use.”

“Frequently these patients have a relapse in the head and neck area. This location is responsible of many symptoms that are difficult to palliate: pain, breath disorder and swallowing difficulties.”

Afatinib is a compound that irreversibly blocks the ErbB family of cell surface receptors, which includes epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), HER3 and HER4. Around 90% of squamous cell carcinomas of the head and neck overexpress EGFR.

In the latest trial, researchers aimed to see if inhibiting multiple ErbB receptors simultaneously would improve the clinical efficacy of EGFR-targeted therapy. They studied 483 patients with recurrent or metastatic head and neck squamous cell carcinoma whose cancer had progressed despite treatment with platinum-based therapy. Overall, 322 patients received 40 mg/day oral afatinib and 161 were given 40 mg/m2/week intravenous methotrexate.

The study met its primary endpoint and afatinib significantly improved progression-free survival versus methotrexate, Machiels said. “Afatinib improved progression-free survival and delayed worsening of symptoms, and it is the first tyrosine kinase inhibitor to demonstrate a significant benefit in this disease.”

The toxicity profile was acceptable and manageable with afatinib : the most frequent grade 3/4 drug-related adverse events were rash/acne (9.7%) and diarrhea (9.4%). Less treatment-related dose reductions, discontinuations and fatal events were seen with afatinib.

“We are pleased with the results because we showed a benefit, although modest, in a very well-designed controlled trial,” Machiels says. “The difference of this trial compared to the others performed in the same setting is that it was a homogenous population. It sets a kind of baseline design that could be used to design further trials.”

The trial was not able to demonstrate that afatinib improves survival. “Many potential reasons could explain why we were not able to demonstrate a survival benefit,” Machiels says. “It could be simply because afatinib does not improve survival. However, 50% of the patients in both arms received subsequent therapies that could have influenced the survival benefit, for example a significant number of patients received subsequent anti-EGFR therapies in the methotrexate arm.”

Future studies should focus on understanding which patient groups derive a clinically meaningful benefit from afatinib, the researchers says. They hope to provide further molecular insights and hypotheses to identify patients who benefit.

“We should hope that based on the new molecular data that is becoming available and through advances in the understanding of the molecular biology of this disease, some new treatments will be investigated in a near future.”

-END-

Notes to Editors

29LBA_PR: Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-Head & Neck 1

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Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.

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29LBA_PR                            Saturday, September 27, 2014 – 09:15 AM – 10:45 AM  - Hall Bilbao

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Abstract: 29LBA_PR

Afatinib versus methotrexate (MTX) as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy: primary efficacy results of LUX-Head & Neck 1

J-P. Machiels1, R.I. Haddad2, J. Fayette3, L.F. Licitra4, M. Tahara5, J.B. Vermorken6, P.M. Clement7, T. Gauler8, D. Cupissol9, J.J. Grau10, J. Guigay11, F. Caponigro12, G. De Castro Jr13, L. De Souza Viana14, U. Keilholz15, J.M. Del Campo16, X.J. Cong17, L. Svensson18, E. Ehrnrooth18, E.E.W. Cohen19on behalf of the LUX-H&N 1 investigators
1Oncology, Cancer Center, Service d’Oncologie Médicale, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, BELGIUM, 2Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School, Boston, MA, USA, 3Medical Oncology, Léon Bérard Center, University of Lyon, Lyon, FRANCE, 4Medical Oncology, Istituto Nazionale Tumori, Milan, ITALY, 5Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, JAPAN, 6Medical Oncology, Antwerp University Hospital, Edegem, BELGIUM, 7Medical Oncology, KU Leuven, Leuven, BELGIUM,8Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, GERMANY, 9Medical Oncology, Institut du Cancer de Montpellier Val d’Aurelle, Montpellier, FRANCE, 10Oncology, Hospital Clínic de Barcelona, Barcelona, SPAIN, 11Medical Oncology, 11 Gustave Roussy, Villejuif, at present Centre Antoine Lacassagne, Nice, FRANCE, 12Head and Neck – Medical Oncology, National Tumor Institute of Naples, Naples, ITALY, 13Clinical Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, BRAZIL, 14Medical Oncology, Hospital de Câncer de Barretos, São Paulo, BRAZIL, 15Medical Oncology, Charité Comprehensive Cancer Center, Berlin, GERMANY, 16Medical Oncology, Hospital Universitario Vall d’Hebron, Barcelona, SPAIN, 17Medical Oncology, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, USA, 18Medical, Boehringer Ingelheim, Danmark A/S, DENMARK, 19Medicine, University of California San Diego Moores Cancer Center, La Jolla, CA, USA

Aim: Patients with R/M HNSCC who progress after first-line platinum-based therapy have a dismal prognosis and no well-defined treatment. Afatinib, an irreversible ErbB family blocker, showed anti-tumor activity in a phase II trial in this setting.

Methods: In this phase III trial, patients with R/M HNSCC after progression on/after platinum-based therapy were randomised 2:1 to 40 mg/day oral afatinib (n=322) or 40 mg/m2/week intravenous MTX (n=161), stratified by ECOG performance status (0/1) and prior use of anti-EGFR antibody therapy (Yes/No) in the R/M setting. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), patient-reported outcomes (PROs) and safety.

Results: Afatinib significantly improved the primary endpoint of PFS vs MTX (median 2.6 vs 1.7 months; HR=0.80 [95% CI 0.65–0.98; p=0.03]), but did not significantly improve OS vs MTX (median 6.8 vs 6.2 months; HR=0.94 [0.75–1.18]). Disease control rate was higher with afatinib vs MTX (49.1% vs 38.5%; p=0.04); ORR was 10.2% vs 5.6% (p=0.10). Tumour shrinkage from baseline was observed in 34.8% of afatinib-treated patients compared to 22.4% of MTX-treated patients. Afatinib delayed deterioration of global health status, pain and swallowing vs MTX (all p≤0.03) and provided improvement in pain (p=0.03). The most frequent grade 3/4 drug-related adverse events were rash/acne (9.7%) and diarrhoea (9.4%) with afatinib, and leukopenia (15.6%) and stomatitis (8.1%) with MTX. Fewer treatment-related dose reductions, discontinuations and fatal events were seen with afatinib. Additional optional biomarker analyses, including p16 status, will be presented.

Conclusions: In this phase III trial, second-line afatinib significantly improved the primary endpoint of PFS and delayed deterioration of PROs vs MTX, with a manageable safety profile, in patients with R/M HNSCC after failure of platinum-based therapy.

Machiels JPH, Haddad RI and Fayette J contributed equally to this work.

Disclosure: J-P. Machiels: Advisory boards for Boehringer Ingelheim, Novartis; R.I. Haddad: Advisory boards for Celgene, Bayer Corporate sponsored research for Boehringer Ingelheim; L.F. Licitra: Advisory boards for Eisai, Bristol-Myers Squibb, GlaxoSmithKline, Merk-Serono, Amgen, Boehringer Ingelheim, Debiopharm, VentiRX, Sobi, F. Hoffmann-La Roche, Celgene; M. Tahara: Advisory boards for Eisai, Boehringer Ingelheim, Otsuka Pharmaceutical Corporate sponsored research for Eisai, Boehringer Ingelheim Other substantive relationships with Merck Serono, Bristol-Myers Squibb; J.B. Vermorken: Advisory boards for Merck Serono, Genentech Other substantive relationships with Steering CIE LUX-H&N 2 trial; P.M. Clement: Advisory boards for Merck Serono, Leo Pharma, Grünenthal Corporate sponsored research for Merck Sharp & Dohme, Grünenthal; T. Gauler: Stock ownership with Bayer AG Advisory boards for Boehringer Ingelheim (BI), Merck Serono, Novartis Corporate sponsored research for BI (ITS), Merck Serono (ITS) Other substantive relationships with BI, Merck Serono; G. De Castro Jr: Advisory boards for Boehringer Ingelheim, Bayer, F. Hoffmann-La Roche, Novartis; X.J. Cong, L. Svensson and E. Ehrnrooth: Other substantive relationships with Employee, Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Keywords: afatinib, methotrexate, Phase III, Head and neck