Drugs Xagena
The FDA ( US Food and Drug Administration ) has approved Tecentriq ( Atezolizumab ) in combination with Avastin ( Bevacizumab ), Paclitaxel and Carboplatin ( chemotherapy ), for the initial ( first-line ) treatment of people with metastatic non-squamous non-small cell lung cancer ( NSCLC ) with no EGFR or ALK genomic tumour aberrations.
The approval is based on results from the phase III IMpower150 study, which showed that Atezolizumab in combination with Bevacizumab and chemotherapy helped people live significantly longer, compared to Bevacizumab and chemotherapy ( median overall survival [ OS] =19.2 versus 14.7 months; hazard ratio [ HR ]=0.78; 95%, CI: 0.64–0.96; p=0.016 ) in the intention-to-treat wild-type ( ITT–WT ) population.
The safety profile of the Atezolizumab combination was consistent with that observed in previous studies.
Roche is working with the FDA on post-marketing commitments to better understand and characterise the potential effects of Atezolizumab-related anti-drug antibodies ( ADAs ) and neutralising antibodies ( NAbs ) across all of the studies.
An analysis of anti-drug antibodies in the IMpower150 study showed no impact on the efficacy of Tecentriq.
Tecentriq is also approved by the FDA to treat people with metastatic NSCLC who have disease progression during or following Platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumour has EGFR or ALK genetic alterations.
IMpower150 is a multicentre, open-label, randomised, controlled phase III study evaluating the efficacy and safety of Atezolizumab in combination with chemotherapy ( Carboplatin and Paclitaxel ) with or without Bevacizumab in people with stage IV or recurrent metastatic non-squamous NSCLC who had not been treated with chemotherapy for their advanced disease.
It enrolled 1,202 people, of whom 1,045 were in the ITT-WT subpopulation, which excluded those people with EGFR and ALK mutations.
People were randomised ( 1:1:1 ) to receive: Atezolizumab plus Carboplatin and Paclitaxel ( Arm A ), or Atezolizumab and Bevacizumab plus Carboplatin and Paclitaxel ( Arm B ), or Bevacizumab plus Carboplatin and Paclitaxel ( Arm C, control arm ).
The co-primary endpoints comparing Arms B and C were overall survival and progression-free survival ( PFS ), as determined by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 ( RECIST v1.1 ) and assessed in the ITT-WT subpopulation. Key secondary endpoints included investigator-assessed progression-free survival, overall survival and safety in the ITT population.
A summary of the ITT-WT data from the IMpower150 study that support this approval is included below:
Atezolizumab in combination with Bevacizumab and chemotherapy helped people live significantly longer, compared to Bevacizumab and chemotherapy ( median OS=19.2 versus 14.7 months; HR=0.78; 95%, CI: 0.64–0.96; p=0.016 ).
In addition, Atezolizumab in combination with Bevacizumab and chemotherapy reduced risk of disease worsening or death ( PFS ) by 29%, compared to Avastin and chemotherapy ( HR: 0.71; 95%, CI: 0.59–0.85, p=0.0002 ).
Atezolizumab in combination with Bevacizumab and chemotherapy shrank tumours ( overall response rate [ ORR ] ) in 55% of people ( 95%, CI: 49–60 ) compared to 42% of people ( 95% CI: 37-48 ) on Bevacizumab and chemotherapy.
4% of people receiving Atezolizumab in combination with Bevacizumab and chemotherapy experienced a complete response ( CR ), and 51% of people experienced a partial response ( PR ).
The median duration of response ( DoR ) for people receiving Atezolizumab in combination with Bevacizumab and chemotherapy was 10.8 months ( 95%, CI: 8.4–13.9 ) compared to 6.5 months ( 95% CI: 5.6-7.6 ) for people on Bevacizumab and chemotherapy.
The most common adverse reactions ( greater than or equal to 20% ) in people receiving Atezolizumab in combination with Bevacizumab and chemotherapy were fatigue and lack of energy ( asthenia; 50% ), hair loss ( alopecia; 48% ), nausea ( 39% ), diarrhoea ( 32% ), constipation ( 30% ), decreased appetite ( 29% ), joint pain ( arthralgia; 26% ), hypertension ( 25% ), and pain from nerve damage ( peripheral neuropathy; 24% ).
There is a strong scientific rationale to support the use of Atezolizumab plus Bevacizumab in combination.
The Atezolizumab and Bevacizumab regimen may enhance the potential of the immune system to combat first-line advanced NSCLC.
Bevacizumab, in addition to its established anti-angiogenic effects, may further enhance Atezolizumab’s ability to restore anti-cancer immunity, by inhibiting VEGF-related immunosuppression, promoting T cell tumour infiltration and enabling priming and activation of T cell responses against tumour antigens.
Atezolizumab is a monoclonal antibody designed to bind with a protein called PD-L1 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.
Bevacizumab is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called vascular endothelial growth factor ( VEGF ) that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis.
Bevacizumab is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour's ability to grow and spread in the body ( metastasise ). ( Xagena )
Source: Roche, 2018
XagenaMedicine_2018
