Durvalumab and Tremelimumab
Findings from a phase 1 expansion study presented at the European Lung Cancer Conference in 2016 demonstrated encouraging activity and favorable toxicity with durvalumab in combination with gefitinib in TKI-naive patients with EGFR-mutant NSCLC.5
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The best objective response rate was 77.8% with gefitinib monotherapy and 80.0% with gefitinib monotherapy followed by concurrent durvalumab plus gefitinib. One patient in the gefitinib arm achieved a complete response while the others had partial responses. Stable disease lasting for 8 weeks or more occurred in 2 and 1 patients in the gefitinib arm and the combination arm, respectively.
Durvalumab is also being evaluated with a checkpoint inhibitor, tremelimumab, which blocks CTLA-4 in patients with locally advanced or metastatic NSCLC. Early results of a phase 1b trial showed that the combination induced a confirmed objective response rate of 23%.6
“Certainly the PD-1 inhibitors and we can pretty safely say the PD-L1 inhibitors have a role in the treating lung cancer, melanoma, bladder cancer, and other malignancies, but the question is, how do we then do our best at combining the different drugs available to get the best value and efficacy without going too far in the way of toxicity and cost?” Dr Masters said.
Durvalumab, a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, blocks the interaction among PD-L1, PD-1, and CD80 with high affinity and selectivity.
Nedaplatin
Nedaplatin is a second-generation platinum compound that is associated with a lower frequency of nausea/vomiting and nephrotoxicity than cisplatin. A phase 3 trial demonstrated significantly longer overall survival with nedaplatin plus docetaxel in contrast with cisplatin plus docetaxel in patients with advanced or relapsed squamous cell carcinoma of the lung.7
Researchers enrolled 355 Japanese patients with stage IIIB/IV squamous NSCLC or postoperative recurrence and randomly assigned them 1:1 to receive nedaplatin 100 mg/m2 IV or cisplatin 80 mg/m2 IV with docetaxel 60 mg/m2 IV every 3 weeks for up to 6 cycles. Results showed that median overall survival was 13.6 months with nedaplatin vs 11.4 months with cisplatin (hazard ratio 0.81; 90% CI, 0.67-0.98; P = .037). Nedaplatin was also associated with a longer progression-free survival than cisplatin (hazard ratio 0.83; 90% CI, 0.69-1.00; P = .050).
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Grade 3 or 4 treatment-related nausea, fatigue, hyponatremia, and hypokalemia were more common in the cisplatin group, while grade 3 or higher neutropenia and thrombocytopenia were more frequent with nedaplatin. There was no difference in grade 3 or higher febrile neutropenia between the 2 treatment arms.
“It is unclear if those differences in efficacy and toxicity will translate to a meaningful improvement in our patients,” Dr Masters said.
