Additive atezolizumab to chemotherapy delays progression in advanced squamous cell carcinoma of the lung
The cancer immunotherapeutic agent atezolizumab appears to improve the prognosis of lung cancer patients when combined with platinum-based chemotherapy. This conclusion is confirmed by the IMpower131 study presented at the annual meeting of the ASCO in Chicago. The humanized PD-L1-antibody was tested in patients with advanced non-small cell lung squamous cell carcinoma (NSCLC).1
Source: ASCO Annual Meeting 2018
One of the study’s primary endpoints is progression-free survival (PFS). This was significantly prolonged in the study by combination with atezolizumab compared to chemotherapy alone (median time to progression 6.3 instead of 5.6 months). 29% of patients had a reduced risk of disease progression according to study data (hazard ratio: 0.71, 95% confidence interval: 0.6-0.85, p = 0.0001).2
As in previous lung cancer studies with atezolizumab, a benefit – in this case combination with the PD-L1 antibody – was observed in all subgroups, including those with low or undetectable PD-L1 expression, says Dr. Robert M. Jotte, study leader, Rocky Mountain Cancer Center, Denver, Colorado, at a press conference during the ASCO Congress. However, those with higher PD-L1 expression profited more. Overall, twice as many patients were progression-free after 12 months under the combination, namely 24.7% compared to 12%.
About the Study
The IMpower131 trial involved 1021 patients with advanced NSCLC. Tumors were tested for PD-L1 expression but patients were included in the study regardless of expression. Patients with EGFR or ALK gene changes in the tumor received targeted treatment prior to initiation of therapy. Although the rate of serious adverse events in combination therapy was higher than with chemotherapy alone (68% vs. 57%), they were consistent with the known safety risks of each therapy.
Improved PFS was observed in all groups of patients who received immunotherapy and chemotherapy, including those with PD-L1-negative tumors and liver metastases. Overall survival data are not yet mature. This is the first phase III trial of an immunotherapy-based combined modality treatment to show a significant improvement in progression-free survival in advanced squamous NSCLC, according to the authors. Although the difference between treatment groups is modest, a statistically significant improvement shows that, overall, people with advanced squamous lung cancer can benefit when immunotherapy is added to standard treatment.
At this interim analysis a statistically significant overall survival (OS) benefit was not observed (median OS was 14 months for atezolizumab plus chemotherapy vs. 13.9 months for chemotherapy alone). Researchers are continuing to follow patients and anticipate a subsequent analysis later this year. More research is needed to determine which patients benefit the most from the addition of immunotherapy to standard chemotherapy.
- ASCO Annual Meeting 2018, 1. bis 5. Juni 2018, Chicago/USA
- Jotte RM et al, Primary PFS and safety analysis of a randomised phase-III study of azetolizumab+carboplatin+paclitaxel or nab-paclitaxel vs. carboplatin+nab-paclitaxel as 1L therapy in advanced squamous NSCLC, #LBA9000