Atezolizumab Combo Approved in UK for Small Cell Lung Cancer

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended atezolizumab (Tecentriq) as a frontline treatment option for patients with extensive-stage small cell lung cancer (ES-SCLC).¹

The positive recommendation was based on findings from the phase 3 IMpower133 trial, in which the combination regimen significantly improved progression-free and overall survival (OS) compared with chemotherapy alone in this patient population. In the intent-to-treat (ITT) population, the atezolizumab plus chemotherapy regimen led to a 30% reduction in the risk of death (HR, 0.70; 95% CI, 0.54-0.91; P = .0069).^2,3 The median OS was 12.3 months and 10.3 months with atezolizumab/chemotherapy and chemotherapy alone, respectively.

Prior draft guidance from NICE recommended against approval of the atezolizumab regimen; however, subsequent negotiations between Roche (Genentech), the manufacturer of atezolizumab, and the NHS England and Improvement, resulted in a lower price for the PD-L1 inhibitor that now qualified as a "cost-effective use of NHS resources."

“We are pleased to be able to recommend this new treatment that could extend the life of patients with this type of lung cancer," Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE, stated in a press release. “I know how important this news will be for patients suffering with this condition, for which there are currently few treatment options. Atezolizumab with carboplatin and etoposide may offer valuable time for patients to spend with their loved ones."

In the international, double-blind, randomized, placebo-controlled phase III IMpower133 study, investigators evaluated the efficacy and safety of frontline atezolizumab added to carboplatin/etoposide in 403 treatment-naïve patients with extensive-stage SCLC.

All patients received four 21-day cycles of carboplatin area under the curve 5 mg/mL/min intravenous (IV) on day 1 and 100 mg/m2 etoposide IV on days 1 through 3. Patients were also randomized 1:1 to receive either concurrent atezolizumab at 1200 mg IV on day 1 (n = 201) or placebo (n = 202) during the induction phase. Treatment was followed by maintenance therapy with atezolizumab or placebo, according to the previous random assignment, every 3 weeks until progressive disease or loss of clinical benefit.

Investigator-assessed progression-free survival (PFS) and OS in the ITT population served as the primary endpoints; secondary endpoints included objective response rate (ORR), duration of response, and safety.

The median age was 64 years (range, 26-90) in both the atezolizumab and placebo groups, and the majority were male (64% vs 65%, respectively), white (81% vs 79%), and former smokers (58.7% vs 61.4%). The atezolizumab arm included 17 patients (8%) with brain metastases and 77 (38%) with liver metastases; while the placebo group consisted of 9% and 36%, respectively.

The median duration of treatment with atezolizumab was 4.7 months, with a median of 7 doses received. The investigators saw no major difference in ORR between arms (60.2% vs 64.4%, respectively) or in median duration of response (4.2 vs 3.9 months).

Results showed that OS events occurred in 51.7% of the atezolizumab arm and 66.3% of the control arm. Atezolizumab was associated with a higher 6-month PFS rate (30.9% vs. 22.4%), and a more than doubling 12-month PFS rate (12.6% vs 5.4%) compared with placebo.

The median PFS was 5.2 months and 4.3 months with atezolizumab/chemotherapy and chemotherapy alone, respectively (HR, 0.77; 95% CI, 0.62-0.96; P = .017).

Moreover, the PD-L1 inhibitor demonstrated superior 6-month (32.2% vs 17.1%) and 12-month (14.9% vs 6.2%) event-free rates. Eighteen patients treated with concurrent atezolizumab had ongoing responses versus 7 patients in the control group.

Regarding safety, the profile of the regimen was consistent with prior studies of the individual agents, with no new findings observed.

Serious adverse events (AEs) occurred in 56.6% of those who received atezolizumab/chemotherapy versus 56.1% of those on chemotherapy alone. The most common AEs (≥20%) in patients receiving the immunotherapy/chemotherapy combination were neutropenia (23%), anemia (14%), decreased neutrophil count (14%) and thrombocytopenia (10%).

Immune-related adverse events (irAEs) were more common with atezolizumab compared with placebo (39.9% vs 24.5%). The most common grade 1/2 irAEs among the atezolizumab and placebo arms included rash (16.7% vs 10.2%, respectively), hepatitis (5.6% vs 4.6%), infusion-related reactions (3.5% vs 4.6%), pneumonitis (1.5% vs 1.5%), and colitis (0.5% vs 0%).

References

1. NICE recommends treatment for type of small-cell lung cancer. Published May 27, 2020. https://bit.ly/3guEzDK. Accessed May 27, 2020.
2. Geyer Jr CE, Huang C-S, Mano MS, et al. Phase III Study of Trastuzumab Emtansine(T-DM1) vs Trastuzumab as Adjuvant Therapy in Patients with HER2-Positive Early Breast Cancer with Residual Invasive Disease after Neoadjuvant Chemotherapy and HER2-Targeted Therapy Including Trastuzumab: Primary Results from KATHERINE (NSABP B-50-I, GBG 77 and Roche BO27938). Presented at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract GS1-10.
3. von Minckwitz G, Huang C-S, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer [published online December 5, 2018]. New Engl J Med. doi: 10.1056/NEJMoa1814017