The FDA ( US Food and Drug Administration ) has approved Tecentriq ( Atezolizumab ) as a first-line treatment for adults with metastatic non-small cell lung cancer ( NSCLC ) whose tumours have high PD-L1 expression ( PD-L1 stained greater than or equal to 50% of tumour cells [ TC greater than or equal to 50% ] or PD-L1 stained tumour-infiltrating [ IC ] covering greater than or equal 10% of the tumour area [ IC greater than or equal to 10% ] ), as determined by an FDA-approved test, with no EGFR or ALK genomic tumour aberrations.
This approval is based on an interim analysis from the phase III IMpower110 study, which showed that Atezolizumab monotherapy improved overall survival ( OS ) by 7.1 months compared with chemotherapy ( median overall survival, OS=20.2 versus 13.1 months; hazard ratio, HR=0.59, 95% CI: 0.40–0.89; p=0.0106 ) in people with high PD-L1 expression ( TC3/IC3-wild-type [ WT ] ).
Safety for Atezolizumab appeared to be consistent with its known safety profile, and no new safety signals were identified.
Grade 3–4 treatment-related adverse events were reported in 12.9% of people receiving Atezolizumab compared with 44.1% of people receiving chemotherapy.
Tecentriq is the first and only single-agent cancer immunotherapy with three dosing options, allowing administration every two, three or four weeks.
In the US, Tecentriq has received four approvals across NSCLC, including as a single agent or in combination with targeted therapies and/or chemotherapies. It is also approved in combination with Carboplatin and Etoposide ( chemotherapy ) for the first-line treatment of adults with extensive-stage small cell lung cancer.
IMpower110 is a randomised, open-label study evaluating the efficacy and safety of Atezolizumab monotherapy compared with Cisplatin or Carboplatin and Pemetrexed or Gemcitabine ( chemotherapy ) in PD-L1-selected, chemotherapy-naïve participants with stage IV non-squamous or squamous NSCLC.
The study enrolled 572 people, of whom 554 were in the intention-to-treat WT population, which excluded people with EGFR or ALK genomic tumour aberrations.
The patients were randomised 1:1 to receive: Atezolizumab monotherapy, until disease progression ( or loss of clinical benefit, as assessed by the investigator ), unacceptable toxicity or death; or Cisplatin or Carboplatin ( per investigator discretion ) combined with either Pemetrexed ( non-squamous ) or Gemcitabine ( squamous ), followed by maintenance therapy with Pemetrexed alone ( non-squamous ) or best supportive care ( squamous ) until disease progression, unacceptable toxicity or death.
The primary efficacy endpoint was overall survival by PD-L1 subgroup ( TC3/IC3-WT; TC2/3/IC2/3-WT; and TC1,2,3/IC1,2,3-WT ), as determined by the SP142 assay test.
Key secondary endpoints included investigator-assessed progression-free survival ( PFS ), objective response rate ( ORR ) and duration of response ( DoR ).
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Atezolizumab may enable the activation of T-cells.
Lung cancer is the leading cause of cancer death globally. Each year 1.76 million people die as a result of the disease; this translates into more than 4,800 deaths worldwide every day.
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. 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. ( Xagena )
Source: Roche, 2020