WCLC 2021 | Neratinib-based combination therapy in HER2-Mutant lung cancer

Bob Li, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the results of PUMA-NER-4201 (NCT01827267) and PUMA-NER-5201 (SUMMIT; NCT01953926) – two international Phase II trials of neratinib-based therapy in patients with HER2-mutant lung cancer. Neratinib, a pan-HER tyrosine kinase inhibitor, is shown to have enhanced activity in HER2-mutant lung cancer models when combined with temsirolimus, an mTOR inhibitor, or trastuzumab, an anti-HER2 antibody. Therefore, neratinib monotherapy was compared to neratinib plus temsirolismus and neratinib plus trastuzumab in the PUMA-NER-4201 and SUMMIT trials, respectively. Results showed that the monotherapy had little activity, with low overall response rates in both trials. Response rates were superior to monotherapy in both combination arms and produced durable responses in a subset of patients. This interview took place during the IASLC World Conference on Lung Cancer (WCLC) virtual meeting 2021.