Atezolizumab Immunotherapy Receives FDA Approval for First-Line Lung Cancer Treatment

On 6 December 2018, the United States Food and Drug Administration (FDA) approved, for stage 4. non-squamous non-small cell lung cancer, atezolizumab (Tecentriq) immunotherapy in combination with bevacizumab, paclitaxel, and carboplatin.

Approval was based on an open-label, randomized (1: 1: 1) trial in metastatic non-squamous non-small cell lung cancer (NSq NSCLC), enrolling 1202 patients in the three-arm IMpower150 clinical trial . Eighty-seven percent (1045 patients) did not have EGFR or ALK mutations. The trial compared each atezolizumab-containing arm with the control arm. Patients were randomized to 3 arms:

• Atezolizumab, carboplatin, paclitaxel , and bevacizumab (4-drug regimen);
• Atezolizumab, carboplatin, and paclitaxel (3-drug regimen); or
• Carboplatin, paclitaxel, and bevacizumab (control arm).

Bevacizumab Enhances Immunotherapy Effectiveness

Bevacizumab (Altuzan) is an intravenously infused monoclonal antibody preventing new tumor blood vessel formation, an anti-angiogenic drug.

Bevacizumab combined with chemotherapy was already approved for metastatic non-squamous NSCLC. In addition to its known anti-angiogenic effects, suppressing vascular endothelial growth factor (VEGF) gives it immunomodulatory (immune-regulating) effects. Adding bevacizumab may enhance atezolizumab by reversing VEGF-mediated immune suppression.

IMpower150 asked two questions: does VEGF blockade enhance immunotherapy, and does immunotherapy combine effectively with chemotherapy?

Below, the design and results of IMpower150 can be seen:

Study Results:

• Among NSq NSCLC patients without EGFR or ALK mutations, estimated median overall survival with the 4-drug regimen was 19.2 months, compared with 14.7 months for carboplatin, paclitaxel, and bevacizumab.
• Adding atezolizumab immunotherapy to the triple regimen reduced mortality risk by %22.
• Estimated median progression-free survival (PFS) with the 4-drug regimen was 8.5 months, compared with 7 months in the control arm. Adding atezolizumab reduced progression risk by %29.
• Overall response rates were, in the 4-drug arm, %55, and in the control arm, %42.
• The 3-drug arm (atezolizumab, carboplatin, paclitaxel) and control arm (carboplatin, paclitaxel, bevacizumab) showed no difference in overall or progression-free survival.
• For patients receiving the 4-drug regimen, the most common adverse effects (in at least % 20) were fatigue, alopecia (hair loss), nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, and neuropathy. Atezolizumab could not be continued in %15 because of adverse effects. Pneumonitis was the most common reason for discontinuation (% 1.8).

The recommended atezolizumab dose is every 3 weeks over 60 minutes intravenously (into a vein) at 1200 mg.