Atezolizumab and chemotherapy approach for NSCLC with squamous epithelial histology

New findings announced in the treatment of advanced non-small cell lung cancer

Patients with advanced non-small cell lung cancer (NSCLC) with squamous epithelial histology may benefit from an additional dose of the PD-L1 inhibitor atezolizumab in addition to chemotherapy in first-line treatment compared to chemotherapy alone. 

The interim results of the Phase-III study “IMpower 131” were presented by Robert M. Jotte from the USON Thoracic Committee at the Rocky Mountain Cancer Centers, Denver, USA, at a June 2nd press conference in the context of the 2018 ASCO Annual Meeting in Chicago. 

In about 25 to 30% of patients with non-small cell lung cancer (NSCLC), the tumor has squamous epithelial histology. Squamous epithelium NSCLC are difficult to treat and there have been few new treatment options in recent decades. Less than 15% of patients survive the first year following diagnosis and less than 2% survive past five years after diagnosis.

Platinum-based (platins) therapy regimes are currently the standard in first-line therapy with advanced tumors. Patients initially treated with carboplatin plus nab-paclitaxel achieved a median progression-free survival (PFS) of 5.6 months, median overall survival (OS) was 10.7 months and objective response rate (ORR) was 41%. In recent studies, NSCLC with non-plate epithelial histology had proven beneficial in combining immunotherapy and chemotherapy.

Phase III study with the PD-L1 inhibitor atezolizumab

Atezolizumab (commercial name: Tecentriq®) is a monoclonal antibody that blocks PD-L1. In the EU, it is currently approved as a monotherapy in adult patients for the treatment of locally advanced or metastatic NSCLC following prior chemotherapy. Patients with activating EGFR mutations or ALK-positive tumor mutations should already have received a therapy targeted to these mutations before therapy with atezolizumab. It may also be used as monotherapy in adult patients for the treatment of locally advanced or metastatic urothelial carcinoma following prior platinum chemotherapy or in patients considered unsuitable for treatment with cisplatin.

Jotte's team is investigating the efficacy and tolerability of atezolizumab in combination with carboplatin and nab-paclitaxel in 1,021 patients with advanced squamous epithelium NSCLC in the open, multicenter, randomized phase-III study “IMpower 131” compared to chemotherapy alone. Patients had not yet received pre-treatment, PD-L1 expression was not an inclusion criterion, but was one of the stratification factors alongside sex and the presence of liver metastases. Patients with activating EGFR mutations or ALK-positive tumor mutations received targeted therapeutics prior to study inclusion. Patients were randomly treated as follows:

The intermediate analysis shows Atezolizumab reduces the risk of progression and death

Jotte presented the data of patients from Arm B (n = 343) and Arm C (n = 340) after a median follow-up of 17.1 months, the results for Arm A are not yet available. Atezolizumab doubled 1-year PFS from 12.0% to 24.7%. Median PFS was 6.3 months (5.7-7.1 months) with atezolizumab plus chemotherapy and 5.6 months (5.5-5.7 months) with chemotherapy alone, reducing the relative risk of progression or death by 29% (hazard ratio 0.71, p = 0.0001). The benefit of atezolizumab was demonstrated in all subgroups, including patients without PD-L1 expression and patients with liver tumors. However, in patients with high PD-L1 expression, the relative risk of progression or death was reduced by 56%, PFS increased from 5.5 months to 10.1 months, and in patients without PD-L1 expression, the risk decreased by 19%. Data on the second primary endpoint, overall survival, are not yet mature. A further interim analysis will be presented in the course of the year.

Side effects were 68% more frequent in the immunotherapy group than in the chemotherapy group with 57%. New, previously unknown adverse effects were not observed. Most common side effects under atezolizumab were rash, colitis and decrease in thyroid hormones.

Jotte RM, et al. IMpower131: Primary PFS and safety analysis of a randomized phase III study
ofatezolizumab + carboplatin + paclitaxel or nab-paclitaxel vs carboplatin + nab-paclitaxel as 1L therapy in advanced squamous NSCLC. 2018 ASCO Annual Meeting, Chicago, June 1-5, 2018, Abstract LBA9000.

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