Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors.
BACKGROUND
Treatment options are scarce in pretreated advanced non-small-cell lung cancer (NSCLC) patients. RAD001, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown phase I efficacy in NSCLC.


METHODS
Stage IIIb or IV NSCLC patients, with two or fewer prior chemotherapy regimens, one platinum based (stratum 1) or both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (stratum 2), received RAD001 10 mg/day until progression or unacceptable toxicity. Primary objective was overall response rate (ORR). Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing.


RESULTS
Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common > or =grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS.


CONCLUSIONS
RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.
Soria
J-C
JC
Lung Cancer Unit, Gustave Roussy Institute, Villejuif, France.
Shepherd
F A
FA
Douillard
J-Y
JY
Wolf
J
J
Giaccone
G
G
Crino
L
L
Cappuzzo
F
F
Sharma
S
S
Gross
S H
SH
Dimitrijevic
S
S
Di Scala
L
L
Gardner
H
H
Nogova
L
L
Papadimitrakopoulou
V
V
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004417:Dyspnea / Q000139:chemically induced; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000068338:Everolimus; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011014:Pneumonia / Q000139:chemically induced; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012044:Regression Analysis; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013280:Stomatitis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus