Detailed primary results from the positive Phase II DESTINY-Lung01 trial of Enhertu (trastuzumab deruxtecan), the AstraZeneca and Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) HER2-directed antibody drug conjugate (ADC), showed a robust and durable tumour response in previously treated patients with HER2-mutant (HER2m) unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC). Results presented during a late-breaking Proffered Paper session at the European Society for Medical Oncology (ESMO) Congress 2021 and simultaneously published in The New England Journal of Medicine confirm Enhertu as the first HER2-directed therapy to show a strong tumour response in this patient population.
Lung cancer is the leading cause of cancer death among both men and women, and accounts for about one-fifth of all cancer deaths globally, with 80-85% classified as NSCLC.1-3 There are currently no medicines approved specifically for the treatment of HER2m NSCLC, which affects approximately 2-4% of patients with NSCLC.4,5
Primary results from the HER2m cohort (cohort 2) of DESTINY-Lung01 in previously treated HER2m NSCLC demonstrated a confirmed objective response rate (ORR) of 54.9% in patients treated with Enhertu (6.4 mg/kg) as assessed by independent central review (ICR). One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed.
A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for Enhertu was 9.3 months. The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.
Bob Li, MD, PhD, MPH, Memorial Sloan Kettering Cancer Center, said: "Despite more than 20 years of research into HER2-mutations in non-small cell lung cancer, there are currently no approved HER2-targeted therapies for non-small cell lung cancer. Patients with HER2-mutant non-small cell lung cancer are associated with younger age, female sex, never smoking history, and a poor prognosis with increased incidence of brain metastases, representing an unmet clinical need. The impressive results from DESTINY-Lung01 showed most patients experienced a reduction in tumour size with Enhertu treatment, suggesting this medicine has the potential to become the new standard of care for these patients."
Susan Galbraith, Executive Vice President, Oncology R&D, said: "Lung cancer is a devastating diagnosis, and for patients with HER2-mutant lung cancer, a targeted treatment for their specific disease has not been an option. These data reinforce the potential of Enhertu to become the first HER2-directed therapy for these patients and reaffirm how this treatment is truly delivering on its transformative potential."
Ken Takeshita, Global Head, Research and Development, Daiichi Sankyo, said: "Enhertu is the first HER2-directed therapy to demonstrate a robust and durable tumour response in patients with HER2-mutant non-small cell lung cancer. This is potentially great news for patients, and we are continuing to conduct research, with the goal of bringing Enhertu to those with this specific form of lung cancer."
Responses were observed across HER2m subtypes, as well as in patients with no detectable HER2 expression or HER2 gene amplification. Efficacy was observed in subgroups including prior treatment with platinum-based therapy, or platinum-based and anti-PD-(L)1 therapy, as well as asymptomatic brain metastases at baseline.
