A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.
Resistance to EGFR tyrosine kinase inhibitors develops in patients with EGFR-mutant lung cancers. New treatments are needed to address resistance not mediated by EGFR T790M; preclinical evidence suggests that the Janus kinase/signal transducers and activators of transcription signaling pathway is important in acquired resistance to EGFR-directed therapy.



We evaluated the toxicity and efficacy of erlotinib and ruxolitinib in patients with EGFR-mutant lung cancers with acquired resistance to erlotinib. Exosomes were analyzed to assess changes in relevant protein expression during treatment.



We enrolled 22 patients: 12 patients in the phase 1 portion of the study and 10 patients in the phase 2 portion. We did not observe any dose-limiting toxicities. The maximum tolerated dose of erlotinib was 150 mg daily and that of ruxolitinib was 20 mg twice daily. The most frequent toxicities (any grade) were anemia, diarrhea, and elevation of liver function test results. One partial response was observed (5% [95% confidence interval: 0-13]). The median progression-free survival was 2.2 months (95% confidence interval: 1.4-4.1).



This is the first study assessing the combination of EGFR and Janus kinase inhibition in patients with EGFR-mutant lung cancers. The combination was well tolerated but ineffective. Exosomal EGFR levels may reflect changes in tumor EGFR expression in response to therapy.
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York. Electronic address: yuh@mskcc.org.
Helena A
HA
Yu
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Leslie
L
Perez
Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Qing
Q
Chang
Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Sizhi P
SP
Gao
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Mark G
MG
Kris
Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Gregory J
GJ
Riely
Breast Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York.
Jacqueline
J
Bromberg
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D011446:Prospective Studies; D011720:Pyrazoles / Q000008:administration & dosage; D011743:Pyrimidines; D015996:Survival Rate
D014408:Biomarkers, Tumor; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
Acquired resistance; EGFR; Erlotinib; JAK; Ruxolitinib; STAT