http://www.ncbi.nlm.nih.gov/pubmed/22949150

J Clin Oncol. 2012 Sep 4. [Epub ahead of print]

Randomized, Phase III Study of Gemcitabine or Erlotinib Maintenance Therapy Versus Observation, With Predefined Second-Line Treatment, After Cisplatin-Gemcitabine Induction Chemotherapy in Advanced Non-Small-Cell Lung Cancer.

Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L,Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B.

Source

Maurice Pérol, Mojgan Devouassoux-Shisheboran, Hospices Civils de Lyon; David Pérol, Céline Ségura-Ferlay, Centre Léon Bérard, Lyon; Christos Chouaid, Hôpital Saint-Antoine; Bernard Milleron, Tenon University Hospital, Paris; Fabrice Barlési, University of Mediterranée-Assistance Publique Hôpitaux de Marseille, Marseille; Radj Gervais, Centre François Baclesse; Gérard Zalcman, Centre Hospitalo-Universitaire Côte de Nacre, Caen; Virginie Westeel, University Hospital, Besançon; Jacky Crequit, Centre Hospitalier de Creil, Creil; Hervé Léna, Centre Hospitalier Universitaire de Rennes, Rennes; Alain Vergnenègre, University Hospital, Limoges; Isabelle Monnet, Centre Hospitalier Intercommunal de Créteil, Créteil; Hervé Le Caer, Centre Hospitalier de Draguignan, Draguignan; Pierre Fournel, Institut de Cancérologie de la Loire, Saint Etienne; Lionel Falchero, Centre Hospitalier de Villefranche, Villefranche; Michel Poudenx, Centre Antoine Lacassagne, Nice; Fabien Vaylet, Hôpital d'Instruction des Armées Percy, Clamart, France; Miquel Taron, Pangaea Biotech, USP Institut Universitari Dexeus, Barcelona, Spain.

Abstract

PURPOSE

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. 

PATIENTS AND METHODS

Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS).

RESULTS

PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. 

CONCLUSION

Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.