Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer.
PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, has shown antitumor activity in gastric cancer in preclinical and phase I studies. This phase II study evaluated the efficacy and safety of everolimus in pretreated patients with advanced gastric cancer. PATIENTS AND METHODS Patients with advanced gastric cancer who experienced progression despite prior chemotherapy received everolimus 10 mg orally daily until disease progression or study discontinuation. The primary end point was disease control rate (DCR; ie, complete response, partial response, or stable disease). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS Fifty-three patients were assessable (median age, 63 years; 51% and 49% received one or two prior chemotherapy regimens, respectively). Although no complete or partial response was obtained, a decrease in tumor size from baseline was observed in 45% of patients by central review. The DCR was 56.0% (95% CI, 41.3% to 70.0%); median PFS was 2.7 months (95% CI, 1.6 to 3.0 months). At a median follow-up time of 9.6 months, median OS was 10.1 months (95% CI, 6.5 to 12.1 months). Common grade 3 or 4 adverse events included anemia, hyponatremia, increased gamma-glutamyltransferase, and lymphopenia. Grade 1 or 2 pneumonitis was reported in eight patients (15.1%). CONCLUSION Everolimus monotherapy resulted in a promising DCR in patients with previously treated advanced gastric cancer. Adverse events are consistent with the reported safety profile of everolimus. These results warrant further evaluation in patients with advanced gastric cancer.
Doi
Toshihiko
T
National Cancer Center Hospital East, 5-1, Kashiwanoha 6-chome, Kashiwa-shi, Chiba 277-8577, Japan. tdoi@east.ncc.go.jp
Muro
Kei
K
Boku
Narikazu
N
Yamada
Yasuhide
Y
Nishina
Tomohiro
T
Takiuchi
Hiroya
H
Komatsu
Yoshito
Y
Hamamoto
Yasuo
Y
Ohno
Nobutsugu
N
Fujita
Yoshie
Y
Robson
Matthew
M
Ohtsu
Atsushi
A
D000328:Adult; D000368:Aged; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D012449:Safety; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus