Europe Adopts Positive Opinion for Combination Therapy of Atezolizumab + Chemo for NSCLC

The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, the counterpart of the United States Food and Drug Administration (FDA), was known as the European Agency for the Evaluation of Medicinal Products or European Medicines Evaluation Agency (EMEA).Following the United Kingdom's decision to withdraw from the European Union in 2017, the European Union (EU) Member States decided to relocate the Agency to Amsterdam, The Netherlands. Since Match 2019 the Agency is operational in the Dutch capital.The Photo shows the Rijksmuseum, in downtown Amsterdam.This file is licensed under the Creative Commons Attribution 3.0 Unported license. Courtesy: Nikolai Karaneschev.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency’s (EMA), based in Amsterdam, The Netherlands, has adopted a positive opinion for atezolizumab (Tecentriq®; Roche/Genentech) in combination with chemotherapy (carboplatin and Abraxane® [albumin-bound paclitaxel; nab-paclitaxel]; Abraxis BioScience, a division of Celgene), for the initial (first-line) treatment of adults with metastatic non-squamous non-small cell lung cancer (NSCLC) who do not have EGFR mutant or ALK-positive NSCLC.

Leading cause of death
Lung cancer is the leading cause of cancer death globally. [1] Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[1] Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.3 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.[2]

Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.[3] receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells.

Atezolizumab is a cancer immunotherapy (CIT) that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

The development of atezolizumab and its clinical programme is based on our greater understanding of how the immune system interacts with tumors and how harnessing a person’s immune system combats cancer more effectively.

Atezolizumab is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive triple-negative breast cancer.

IMpower130
The decision by the European regulator is primarily based on results from the Phase III IMpower130 study (NCT02367781) , which demonstrated that the atezolizumab combination therapy helped people live significantly longer, compared with chemotherapy alone (median overall survival [OS]=18.6 versus 13.9 months; hazard ratio [HR]=0.79; 95% CI: 0.64–0.98; p=0.033) in the intention-to-treat (ITT) population.[3]

The atezolizumab-based combination also significantly reduced the risk of disease worsening or death (progression-free survival, PFS) compared with chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001) in the ITT-WT population.[3]

The safety profile of the atezolizumab combination therapy was consistent with that observed in previous studies.

Sandra Horning, MD, Roche
Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.

“We are pleased to receive a positive opinion from the CHMP for this atezolizumab-based lung cancer combination for people living with non-squamous non-small cell lung cancer,” noted Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.

“Lung cancer is a complex disease that requires a range of treatment options. We are now one step closer to providing another important alternative for this difficult-to-treat form of cancer,” Horning added.

Despite recent advances in the treatment of NSCLC, there is still a need for new options to support a tailored approach to treatment of this complex disease. Lung cancer is the leading cause of cancer death globally.[1]

Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.[1]

Based on the CHMP positive opinion, a final decision regarding the approval of this atezolizumab-based combination is expected from the European Commission in the near future.

IMpower130 is a Phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of atezolizumab in combination with carboplatin and nab-paclitaxel versus chemotherapy (carboplatin and nab-paclitaxel) alone for chemotherapy-naïve patients with stage IV non-squamous NSCLC. The study enrolled 723 people who were randomised (2:1) to receive:

  • Atezolizumab + carboplatin and nab-paclitaxel (Arm A), or
  • Carboplatin and nab-paclitaxel (Arm B, control arm)

During the treatment-induction phase, people in Arm A received atezolizumab and carboplatin on day 1 of each 21-day cycle, and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until loss of clinical benefit, whichever occurred first. People received atezolizumab during the maintenance treatment phase until loss of clinical benefit was observed.

During the treatment-induction phase, people in Arm B received carboplatin on day 1 and nab-paclitaxel on days 1, 8 and 15 of each 21-day cycle for 4 or 6 cycles or until disease progression, whichever occurred first. People received best supportive care during the maintenance treatment phase. Switch maintenance to pemetrexed was also permitted. People who were consented prior to a protocol revision were given the option to crossover to receive atezolizumab as monotherapy until disease progression.

The co-primary endpoints were:

PFS, as determined by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT population
OS in the ITT-WT population

A summary of the ITT data from the IMpower130 study that support this recommendation:[3]

  • Atezolizumab in combination with chemotherapy helped people live significantly longer, compared with chemotherapy alone (median OS=18.6 versus 13.9 months; HR=0.79; 95% CI: 0.64–0.98; p=0.033).
  • Atezolizumab in combination with chemotherapy significantly reduced the risk of disease worsening or death (PFS) by 36% compared with chemotherapy alone (median PFS=7.0 versus 5.5 months; HR=0.64; 95% CI: 0.54–0.77; p<0.0001).
  • Atezolizumab in combination with chemotherapy shrank tumours (overall response rate [ORR]) in 49.2% of people (95% CI: 44.49–53.96) compared with 31.9% of people (95% CI: 25.84–38.36) on chemotherapy alone.

The median duration of response (DoR) for people receiving atezolizumab in combination with chemotherapy was 8.4 months (95%, CI: 6.9–11.8) compared with 6.1 months (95% CI: 5.5–7.9) for people on chemotherapy alone.

Grade 3-4 treatment-related adverse events (AEs) were reported in 73.2% of people receiving atezolizumab plus chemotherapy compared to 60.3% of people receiving chemotherapy alone. The most common Grade 3 – 4 AEs in people receiving atezolizumab plus chemotherapy were an abnormal low count of a certain type of white blood cell (neutropenia, 32.1%), a decrease in red blood cells (anaemia, 29.2%) and decreased neutrophil count (12.1%).

Clinical trials
A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (IMpower130) | NCT02367781

Reference
[1] GLOBOCAN 2018; Lung Cancer: Estimated cancer incidence, mortality and prevalence worldwide. World Health Organization. Online. Last accessed July 28, 2019.
[2] American Cancer Society; What Is Non-Small Cell Lung Cancer? Online. Last accessed July 28, 2019.
[3] Capuzzo F et al. IMpower130: Progression-free survival (PFS) and safety analysis from a randomised phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab (atezo) as first-line (1L) therapy in advanced non-squamous NSCLC. Presented at: European Society for Medical Oncology’s (ESMO) 2018 Conference on 22 October 2018, Munich, Germany. Abstract #LBA53.