On 27 September at the European Society for Medical Oncology (ESMO 2019) conference, interim results from the highly-anticipated Phase III IMpower110 study were presented.
Results demonstrated that first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and high programmed cell death ligand-1 (PD-L1) expression who used Roche’s Tecentriq (atezolizumab) monotherapy resulted in improved overall survival (OS) compared with platinum-based chemotherapies, cisplatin or carboplatin and pemetrexed or gemcitabine, alone.
These results demonstrate the expanding potential of first-line Tecentriq monotherapy in NSCLC patient populations, providing an additional treatment option for physicians and patients. Roche will submit these data to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), to accelerate discussions on patient access to this treatment option.
Tecentriq is a monoclonal antibody which binds to PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, inhibiting its interactions with both PD-1 and B7.1 receptors to enable the re-activation of T-cells. At present in NSCLC, Tecentriq monotherapy is only approved for the treatment of metastatic NSCLC patients with disease progression during or following platinum-based chemotherapy. Tecentriq is also approved in combination with bevacizumab and chemotherapy, such as carboplatin and paclitaxel, in first-line treatment of metastatic non-squamous NSCLC with no EGFR or ALK mutations.
PD-L1 subgroups were determined by an assessment of tumour cell (TC) and tumour-infiltrating immune cells (IC) levels. Compared to chemotherapy alone, Tecentriq monotherapy was statistically significant in improving OS by 7.1 months in patients with high PD-L1 expression, stated as the TC3/IC3-WT population (≥50% TC or ≥10% IC). Investigator-assessed progression-free survival (PFS) for Tecentriq was demonstrated at a median of 8.1 months compared to 5.0 months for chemotherapy alone, objective response rate (ORR) at 38.3% compared to 28.6%, and a median duration of response (DoR) at 29.3 months compared to 23.9 months. Further, the safety profile was consistent with prior observations.
Anti-PD-1 monotherapy or PD-L1/PD-1 inhibitors in combination with platinum-based doublet chemotherapy, with or without Avastin (bevacizumab) are first-line standards of care in metastatic NSCLC. Merck’s Keytruda, approved in April 2019 for the first-line treatment of metastatic NSCLC patients with high PD-L1 expression (≥50%), stands as Tecentriq’s main competitor in this patient population. Tecentriq’s clinical trials differ in the patient selection criteria due to the evaluation of PD-L1 expression on both tumour cells and tumour-infiltrating immune cells. However, coming into the market in second place, the question stands as to how Roche will further differentiate Tecentriq from its competitors.
Roche has an extensive development programme for Tecentriq, which is currently being evaluated as a monotherapy or in combination with other therapies in nine pipeline lung cancer studies. Should these demonstrate synergistic efficacy in addition to a tolerable safety profile, Roche will successfully differentiate the latecomer product in the increasingly congested NSCLC immuno-oncology space. Further, with approvals in the treatment of locally advanced or metastatic urothelial cancer and in PD-L1-positive metastatic triple-negative breast cancer, Tecentriq shows huge potential across a broad range of cancers which are also being investigated, such as bladder, breast, colorectal, gastric, liver, ovarian, pancreatic, renal and, head and neck cancers.
GlobalData (2016). EpiCast Report: Non-Small Cell Lung Cancer (NSCLC) – Epidemiology Forecast to 2025, November 2016, GDHCER132-16
GlobalData (2016). PharmaPoint: Non-Small Cell Lung Cancer (NSCLC) – Global Drug Forecast and Market Analysis to 2025, November 2016, GDHC134PIDR