Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer.
OBJECTIVE
To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer.


METHODS
Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were naive to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status.


RESULTS
Overall median TTP was 6.4 months (95% CI [2.7-11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80-100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8-17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80-100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80-100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopenia, and abdominal pain, and most were of grades 1-2 severity.


CONCLUSIONS
The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial.
Mitry
Emmanuel
E
Hépato-gastroentérologie et oncologie digestive, Assistance Publique des Hôpitaux de Paris, Hôpital Ambroise Paré, 92104, Boulogne Billancourt, France.
Hammel
Pascal
P
Deplanque
Gaël
G
Mornex
Françoise
F
Levy
Philippe
P
Seitz
Jean-François
JF
Moussy
Alain
A
Kinet
Jean-Pierre
JP
Hermine
Olivier
O
Rougier
Philippe
P
Raymond
Eric
E
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines; D011725:Pyridines; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D010880:Piperidines; D011725:Pyridines; D013844:Thiazoles; D003841:Deoxycytidine; C526575:masitinib; D000093542:Gemcitabine