The immune system plays an important role in the development and progression of many cancers, including lung cancer.1,2 Immunotherapies may have activity across broad non-small-cell lung cancer (NSCLC) patient populations by activating the adaptive immune system, including through blockade of immune checkpoint pathways.1,3
Erlotinib (ERL) is US Food and Drug Administration–approved for the first-line treatment of epidermal growth factor receptor mutated (EGFR-MT) NSCLC, with a median progression-free survival (PFS) of 10.4 months.4 Nivolumab (NIV), a PD-1 immune checkpoint inhibitor antibody, has demonstrated encouraging safety and survival outcomes as monotherapy in patients with advanced NSCLC. In light of preclinical data that support EGFR pathway activation of PD-L1 expression and immune escape in EGFR-driven lung tumors,5,6 Rizvi and colleagues undertook a phase 1 study evaluating NIV + ERL in chemotherapy-naïve patients with EGFR-MT advanced NSCLC (ASCO 2014; Abstract 8022). Interim findings were presented for 21 patients enrolled in this study.
The phase 1 study enrolled stage IIIB and stage IV EGFR-MT chemotherapy-naïve NSCLC patients who were either EGFR tyrosine kinase inhibitor (TKI) naïve or who had progression after prior TKI therapy. They received NIV 3 mg/kg (every 2 weeks) plus ERL (150 mg daily by mouth) until disease progression or unacceptable toxicity. Objective response rate (ORR) and PFS were evaluated by RECIST 1.1.
Of the 21 patients who received the NIV + ERL combination, only 1 had not received prior EGFR TKI therapy. Their median age was 63 years, and most (95%) had metastatic disease. All had nonsquamous histology and were EGFR-MT positive.
Any-grade treatment-related adverse events (AEs) were reported in 100% of the 21 patients. Treatment-related grade 3 AEs occurred in 5 patients (24%) and included increased aspartate aminotransferase (AST; n = 2) or alanine transaminase (n = 1), and diarrhea (n = 2). Two patients discontinued NIV + ERL due to treatment-related AEs (grade 3 AST increase, and grade 2 nephritis). No pneumonitis (any grade) was observed.
The ORR was 19% (4 of 21 patients, all partial responses [PRs]), and the 24-week PFS rate was 47%. Median duration of response (DOR) has not been reached (range, 6.1+ to 27.1+ weeks). Of the 20 patients who had relapsed after ERL, 3 (15%) achieved PR, all of which were ongoing at the time of data analysis (DOR, 6.1+, 16.3+, and 27.1+ weeks, respectively). Nine patients (45%) had stable disease with 3 of 9 ongoing. One patient had an unconventional “immune-related” response (ongoing), with 46% reduction in target lesions after progression in nontarget lesions. The EGFR TKI-naïve patient achieved PR with DOR 24.3+ weeks (ongoing).
These interim results suggest that NIV + ERL provide durable clinical benefit and an acceptable safety profile in TKI-refractory EGFR-MT advanced NSCLC. These data support further evaluation of NIV in patients with EGFR-MT NSCLC.
1. Shepherd FA, et al. Immunotherapy for non-small cell lung cancer: novel approaches to improve patient outcome. J Thorac Oncol. 2011;6:1763-1773. 2. Kerkar SP, Restifo NP. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 2012;72:3125-3130. 3. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480-489. 4. Tarceva (erlotinib) [prescribing information]. Northbrook, IL: OSI Pharmaceuticals, LLC; April 2014. 5. Akbay EA, Koyama S, Carretero J. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3:1355-1363. 6. Rech AJ, Vonderheide RH. Dynamic interplay of oncogenes and T cells induces PD-L1 in the tumor microenvironment. Cancer Discov. 2013;3:1330-1332.
