MPDL3280A plus Bevacizumab, with or without Chemotherapy, in Advanced Solid Tumors
Inhibition of the programmed death-1 receptor (PD-1)/PD-ligand 1(PD-L1) immune checkpoint pathway is a novel immunotherapeutic approach that is showing considerable promise in different tumor types. MPDL3280A is an anti–PD-L1 human monoclonal antibody that specifically prevents binding to its receptor PD-1 on activated T cells. Based on the hypothesis that VEGF blockade may synergize with immunotherapy, and that chemotherapy may potentiate immune responses, a recent phase 1b study evaluated the safety and antitumor activity of MPDL3280A in combination with bevacizumab, with or without chemotherapy, in patients with locally advanced or metastatic solid tumors (Lieu et al. ESMO 2014:Abstract A1049O ).
In this open-label study, patients were enrolled in 1 of 2 treatment arms—MPDL3280A 20 mg/kg every 3 weeks plus bevacizumab 15 mg/kg every 3 weeks in patients with refractory tumors or with 1L renal-cell carcinoma (RCC; arm A), or MPDL3280A 15 mg/kg every 2 weeks plus bevacizumab 10 mg/kg every 2 weeks plus FOLFOX at standard doses in patients with oxaliplatin-naive tumors (arm B).
A total of 35 patients in arm A and 36 patients in arm B received treatment, the majority of them had a colorectal cancer (CRC) diagnosis (40% and 83%, respectively). The incidence of grade 3 or 4 adverse events was 49% in arm A and 67% in arm B, and those attributable to MPDL3280A were 3% and 17%, respectively. In arm A, grade 3 or 4 adverse events, regardless of attribution, included abdominal pain (9%), hypertension (9%), hyperbilirubinemia (6%), pneumonia (9%), and tumor pain (6%); in arm B, these included neutropenia (39%) and diarrhea (11%), and an increase in AST (8%). In the arm A cohort, RECIST responses were observed in 40% of patients with 1L RCC and 8% in patients with CRC; in the arm B cohort, responses were reported in 36% of patients with CRC and in 44% of patients with 1L CRC.
These preliminary results demonstrated that MPDL3280A combination therapy with bevacizumab plus chemotherapy confers antitumor activity and is well tolerated, without exacerbation of known toxicities of bevacizumab and FOLFOX, and this may be a promising treatment in patients with advanced or metastatic solid tumors.