Erlotinib ( Tarceva ) is FDA-approved for the first-line treatment of EGFR mutant non-small cell lung cancer ( NSCLC ), with a median progression free survival ( PFS ) of 10.4 months.
Nivolumab, a fully human IgG4 programmed death-1 ( PD-1 ) immune checkpoint inhibitor antibody, has demonstrated encouraging safety and survival outcomes as monotherapy in patients with advanced non-small cell lung cancer.
Preclinical data support EGFR pathway activation of PD-L1 expression and immune escape in EGFR driven lung tumors.
Interim results from a phase I study evaluating Nivolumab plus Erlotinib in an EGFR mutant advanced NSCLC cohort are reported.
Stage IIIB/IV EGFR mutant chemotherapy-naïve NSCLC patients ( EGFR TKI naïve or progression post prior TKI therapy ) received Nivolumab 3 mg/kg IV Q2W plus Erlotinib 150 mg PO daily until progression / unacceptable toxicity.
Objective response rate ( ORR ) and progression-free survival were evaluated by RECIST 1.1.
All patients ( n=21) began study treatment 10 months or more prior to data analysis; only 1 patient was EGFR TKI naïve.
Any-grade treatment-related adverse reactions were reported in all 21 patients; treatment-related grade 3–4 adverse events ( 4 patients ) were increased AST ( n=2 ) or ALT ( n=1 ), weight decrease and diarrhea ( 1 patient each ); 2 patients discontinued due to treatment-related adverse effects ( grade 3 AST increase and grade 2 nephritis ).
No pneumonitis ( any grade ) was observed.
Objective response rate was 19% ( 4/21 patients ) and 24 week progression-free survival rate was 47%; median duration of response ( DOR ) was not reached.
Of the 20 patients with acquired Erlotinib resistance, 3 ( 15% ) achieved partial response ( PR, all ongoing ); 9 patients ( 45% ) had stable disease with 3/9 ( 33% ) ongoing, and 1 patient had an unconventional immune related response ( ongoing ), with 46% reduction in target lesions after progression in non-target lesions.
The EGFR TKI-naïve patient achieved partial response with DOR 24.3+ weeks ( ongoing ).
These interim results suggest that Nivolumab plus Erlotinib may provide durable clinical benefit and an acceptable safety profile in tyrosine-kinase inhibitor ( TKI ) refractory, EGFR mutant advanced non-small cell lung cancer, supporting further evaluation of Nivolumab in patients with EGFR mutant NSCLC. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Meeting, 2014