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The European Medicines Agency’s Committee for Medicinal Products for Human Use has granted a positive opinion to the triplet regimen of atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) for the first-line treatment of patients with advanced, nonsquamous non–small cell lung cancer who do not have EGFR or ALK molecular aberrations.
Sandra Horning, MD
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion to the triplet regimen of atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) for the first-line treatment of patients with advanced, nonsquamous non—small cell lung cancer (NSCLC) who do not have EGFR or ALK molecular aberrations.1
The recommendation is based on interim data from the phase III IMpower130 study, which showed that the combination of atezolizumab/chemotherapy led to a median overall survival of 18.6 months compared with 13.9 months for chemotherapy alone in the intent-to-treat (ITT)—wild-type (WT) population (HR, 0.79; 95% CI, 0.64-0.98; P = .033).2
Regarding safety, the atezolizumab regimen was consistent with what has been observed in prior trials. The European Commission will now make a decision on the approval in the near future, stated Roche, the manufacturer of atezolizumab, in a press release.
“We are pleased to receive a positive opinion from the CHMP for this Tecentriq-based lung cancer combination for people living with non-squamous non-small cell lung cancer,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Roche, stated in the press release. “Lung cancer is a complex disease that requires a range of treatment options. We are now one step closer to providing another important alternative for this difficult-to-treat form of cancer.”
In the multicenter, open-label, IMpower130 trial, patients were randomized 2:1 to receive the atezolizumab triplet as induction therapy followed by maintenance atezolizumab, or chemotherapy alone followed by best supportive care or pemetrexed every 3 weeks as maintenance. Atezolizumab was administered until investigator-assessed loss of clinical benefit or toxicity, while chemotherapy was given until progressive disease or toxicity. Gender, baseline liver metastases, and PD-L1 expression were the stratification factors.
The coprimary endpoints were progression-free survival (PFS) as assessed by investigator using RECIST v1.1 in patients with EGFR or ALK mutations in the ITT-WT population, and OS in the ITT-WT population.
Findings of the interim analysis also showed that the 1- and 2-year OS rates with atezolizumab were 63.1% and 39.6% versus 55.5% and 30.0% in the carboplatin/nab-paclitaxel arm in the ITT-WT group.
Additionally, there was also an improvement in PFS with the atezolizumab combination; the median PFS was 7.0 months (95% CI, 6.2-7.3) and 5.5 months (95% CI, 4.4-5.9) for carboplatin/nab-paclitaxel alone (HR, 0.64; 95% CI, 0.54-0.77; P <.0001). The 6- and 12-month PFS rates also favored atezolizumab at 56.1% and 29.1% versus 42.5% and 14.1% with chemotherapy.
Moreover, the overall response rate (ORR) and median duration of response was 49.2% and 8.4 months (6.9-11.8) with the atezolizumab regimen versus 31.9% and 6.1 months (5.5-7.9) with chemotherapy (P = .0004). In the atezolizumab arm, the ORR consisted of a 2.5% complete response rate, 46.8% partial response rate, 30.4% stable disease rate, and 11% progressive disease rate. Responses were ongoing in 36.8% of patients on atezolizumab and 19.4% on chemotherapy.
The PFS benefit was observed across all prespecified subgroups, except for those with liver metastases (HR, 0.93; 95% CI, 0.59-1.47); this group also did not experience an OS benefit (HR, 1.04; 95% CI, 0.63-1.72).
The PFS and OS benefits varied in the EGFR/ALK-positive subgroups; the median PFS was 7.0 months and 6.0 months with atezolizumab and carboplatin/nab-paclitaxel alone (HR, 0.75; 95% CI 0.36-1.54), respectively; median OS was 14.4 months and 10.0 months (HR, 0.98; 95% CI, 0.41-2.31).
PFS data were also reported by levels of high, low, and negative PD-L1 expression: high (6.4 vs 4.6 months; HR, 0.51; 95% CI, 0.34-0.77), low (8.3 vs 6.0 months; HR, 0.61; 95% CI, 0.43-0.85), and negative (6.2 vs 4.7 months; HR, 0.72; 0.56-0.91). For OS, the benefit was similar: high (17.3 vs 16.9 months; HR, 0.84; 95% CI, 0.51-1.39), low (23.7 vs 15.9 months; HR, 0.70; 95% CI, 0.45-1.08) and negative (15.2 vs 12.0 months; HR, 0.81; 95% CI, 0.61-1.08).
Regarding safety, grade 3/4 treatment-related adverse events (AEs) were reported in 73.2% of patients who received the atezolizumab regimen compared with 60.3% of those who received chemotherapy alone. AEs of special interest include colitis (n = 5), hypothyroidism (n = 3), hepatitis (n = 2), and diabetes mellitus (n = 2). Serious grade 3/4 TRAEs were doubled in the atezolizumab arm at 23.7% versus 12.9%, and AEs that led to dose interruptions occurred in 85.0% and 80.2% of patients.
In January 2019, the FDA accepted a supplemental biologics license application for atezolizumab, carboplatin, and nab-paclitaxel as a first-line treatment for patients with metastatic nonsquamous NSCLC. The FDA is scheduled to make a decision by September 2, 2019.