Atezolizumab and nivolumab prolong overall survival compared with docetaxel in NSCLC
Atezolizumab and nivolumab both produce similar, higher improvements in overall survival compared to docetaxel in NSCLC patients
Atezolizumab and nivolumab have been found to prolong overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) cancer say researchers from Hoffmann-La Roche, Basel, Switzerland. NSCLC accounts for 85% of all lung cancers although nearly 40% of patients are diagnosed at stage 4, which has a poor prognosis, warranting systemic therapy. Treatment of NSCLC can be achieved with platinum-based chemotherapy although many patients relapse and in such cases, mono-therapy with the chemotherapeutic agent, docetaxel, has been found to be effective.
In recent years it has been discovered that developing tumours are capable of evading the immune system by avoiding checkpoint signals designed to prevent uncontrolled activation of T lymphocytes. Monoclonal antibodies including nivolumab and atezolizumab, work to either inhibit checkpoint PD-1 surface receptors (nivolumab) or its ligand, PD-L1 (atezolizumab) thereby blocking these receptors and signals, enabling the immune system to combat the tumour. Although both monoclonal antibodies are approved for use in NSCLC, there is a lack of head-to-head studies comparing these two agents even in comparison to docetaxel.
For the present study, researchers examined real-world studies contained within the US nationwide electronic health record, in which patients with advanced NSCLC and prior platinum-based therapy, who had been started on either atezolizumab, nivolumab or docetaxel. They included adults (18 years and over) diagnosed with locally advanced and/or metastatic NSCLC, none of whom had been previously treated with one of the three agents. The team also only included patients with at least 6 months of follow-up data and set the primary endpoint as overall survival.
In total, 3336 patients were included in the analysis with 206 receiving atezolizumab, 500 docetaxel and 2630 nivolumab. Patients in the atezolizumab and nivolumab groups were of a similar mean age, 68.3 and 67.3 years respectively while those in the docetaxel group were slightly younger with a mean age of 65.6 years.
Compared to docetaxel, use of atezolizumab was associated with a significantly longer survival (adjusted hazard ratio, aHR = 0.79, 95% CI 0.64 – 0.97, p = 0.02) even among those with different cancer stages. In contrast, the adjusted hazard ratio for atezolizumab compared with nivolumab was 1.07 (95% CI 0.89 – 1.28, p = 0.47) and this did not differ between patients at different cancer stages. However, the authors recognised that their analysis may not have been sufficiently powered to detect a difference between these two treatments.
The authors concluded that their real-world data suggested that atezolizumab and nivolumab produced a longer overall survival than docetaxel among those who had failed to respond to platinum-based chemotherapy.
Ramagopalan S et al. Comparative Effectiveness of Atezolizumab, Nivolumab, and Docetaxel in Patients With Previously Treated Non–Small Cell Lung Cancer. JAMA Netw Open 2021
NICE recommends atezolizumab for metastatic urothelial cancer
Atezolizumab has been approved by NICE for untreated advanced or metastatic urothelial cancer in adults where PD-L1 levels exceed 5%.
Urothelial carcinoma is the most common form of bladder cancer, accounting for more than 90% of all bladder cancers in the UK. The main symptom is haematuria in around 80% of cases although other symptoms include increased frequency of urination, pain or a burning sensation when passing urine and weight loss. According to Cancer Research UK, between 2016 and 2018, there were approximately 10,300 new cases of bladder cancer in the UK every year.
Atezolizumab is licensed as mono-therapy for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma, either after prior platinum-containing chemotherapy, or in patients who are cisplatin ineligible and whose tumours have a PD-L1 expression ≥ 5%. The checkpoint protein, programmed death-ligand 1 (PD-L1) which is present on the surface of tumour cells, normally binds to programmed death-1 (PD-1) on the surface of T-cells and prevents the T-cells from killing the tumour cells. Atezolizumab is a checkpoint inhibitor that prevents the binding of PD-L1 to PD-1 and thus restores tumour T-cell activity.
Clinical efficacy
Patients with advanced and metastatic urothelial carcinoma have a poor prognosis with 5-year survival rates as low as 6%. The standard treatment is cisplatin-based chemotherapy however, in a 2017 study 119 previously untreated patients who were cisplatin ineligible, were given atezolizumab at a dose of 1200 mg every 3 weeks until progression. The primary outcome was an objective response and which occurred in 23% of patients and a complete response was seen in 9%. The approval by NICE was based on more data, which came from IMvigor130, a multi-centre, Phase III trial, in which 1213 patients were randomised to either atezolizumab plus platinum-based chemotherapy, atezolizumab mono-therapy or placebo plus platinum-based chemotherapy. In its appraisal, NICE only considered a subgroup of 93 people, with untreated PD-L1-positive (tumour expression of 5% or more) locally advanced or metastatic urothelial cancer and who were ineligible to be treated with cisplatin.
The median overall survival was 18.6 months for atezolizumab and 10.0 months for platinum-based chemotherapy. The stratified hazard ratio was 0.50 (95% CI 0.29 to 0.87, p=0.0125), indicating that treatment with atezolizumab was associated with a significant improvement in overall survival compared with platinum-based chemotherapy. Moreover, the median progression-free survival for atezolizumab was 6.4 months compared with 6.0 months for platinum-based chemotherapy.
In its final appraisal document, NICE stated that "atezolizumab meets NICE's criteria to be considered a life-extending treatment at the end of life. The cost-effectiveness estimates are likely to be within what NICE considers an acceptable use of NHS resources. So atezolizumab is recommended."
Source. NICE 2021