First results from the global Phase III CheckMate-648 study evaluating the efficacy and safety of Opdivo (nivolumab) plus Yervoy (ipilimumab) (NIVO + IPI), or Opdivo plus chemotherapy (NIVO + chemo), versus chemotherapy alone as the first-line treatment for advanced oesophagal squamous cell carcinoma (ESCC), were presented at the virtual 2021 Annual American Society of Clinical Oncology conference (ASCO 2021), held from 4-8 June.
ESCC has a high incidence rate worldwide, constituting almost 90% of the 456,000 oesophagal cancer cases diagnosed each year. Chemotherapy is the mainstay of treatments for patients in recurrent or metastatic settings. Standard first-line chemotherapy for advanced or metastatic ESCC carries a poor prognosis, providing a limited advantage with a median survival of around ten months.
CheckMate-648 evaluated the efficacy and safety of an immunotherapy (IO)/IO combination, along with an IO/chemotherapy combination, compared to standard chemotherapy in advanced ESCC. Upon analysis, both combinations provided a statistical benefit in the primary endpoints, overall survival (OS) and progression-free survival (PFS). Benefit in programmed death-ligand 1 (PD-L1) positive patient populations (defined as >1%) and all-comers may lead to greater patient shares if the label encompasses the intent-to-treat population. In addition, the benefit of having the first dual immunotherapy combination to demonstrate an OS benefit in ESCC may be that it is potentially preferable for patients due to the chemotherapy exclusion from the regimen, despite an inferior benefit compared to NIVO + chemo.
The median duration of treatment was 5.7 months for the NIVO + chemo combination, 2.8 months for the NIVO + IPI combination, and 3.4 months for standard chemotherapy. Upon analysis, the NIVO + chemo arm reported a 46% reduction in the risk of death, 15.4 months median OS with a 6.3-month improvement in tumour cells expressing PD-L1 of 1% or above, and 13.2-month median OS with a 2.5-month improvement in all randomised populations compared with standard chemotherapy, with a median OS of 9.1 months and 10.7 months in these two subpopulations respectively. This presents a key advancement in the treatment selection and administration in advanced or metastatic settings. Longer durations of responses, at 11 months average, were reported with the IPI + NIVO combination. The majority of the treatment-related adverse events were of Grade I or II nature, with no new safety signals being identified with the IO therapies.
These clinically meaningful statistics highlight superior efficacy and durable responses for Opdivo when used in combination with chemotherapy or Yervoy. With positive data from the CheckMate-648 study, Opdivo can be expected to receive US Food and Drug Administration (FDA) approval for use in first-line advanced ESCC, followed by US launch in the third quarter of the year. With reported revenue of $6.9bn worldwide and $3.95bn in the US market last year for Opdivo, this approval will further increase product uptake and boost revenues this year and beyond. This trial success represents a new potential standard of care in the first line, with a favourable safety profile and first-mover advantage in advanced ESCC.