NICE Cites Cost in Deciding Against Atezolizumab for Frontline Advanced Small Cell Lung Cancer

lung cancer

The United Kingdom’s National Institute for Health and Care Excellence (NICE) did not recommend granting marketing authorization to atezolizumab (Tecentriq) in combination with carboplatin and etoposide for the treatment of patients with treatment-naïve extensive-stage small cell lung cancer (ES-SCLC).¹

In its appraisal consultation document, the agency explained that while the combination is suggested to improve overall survival (OS), patients in the National Health Service (NHS) in England are likely to have poorer performance status compared with the IMpower133 study patient population this regimen was evaluated in.

Additionally, the long-term survival benefit of atezolizumab is not yet known. Therefore, NICE noted, the cost-effectiveness estimates comparing the PD-L1 inhibitor plus chemotherapy with chemotherapy alone are uncertain.

“Atezolizumab meets NICE's criteria to be considered a life-extending treatment at the end of life,” the agency stated in the consultation document. “Even so, the cost-effectiveness estimates for atezolizumab with chemotherapy are higher than what is considered a cost-effective use of NHS resources. So, atezolizumab with carboplatin and etoposide is not recommended for untreated extensive-stage small cell lung cancer.”

The list price of atezolizumab is £3807.69 ($5013.49) per 1200 mg vial; the mean treatment cost of a course of treatment for a patient with ES-SCLC is £32,798.39 ($43,184.82) for atezolizumab at list price, £76.18 for carboplatin ($100.30), and £30.89 ($40.67) for etoposide.

The recommendation against authorization is not intended to affect treatment with the atezolizumab regimen that was started in the NHS prior to the publication of this guidance. Patients may continue treatment until patients and/or their clinicians choose to stop the therapy.

In March 2019, the FDA approved the combination of atezolizumab with carboplatin and etoposide for the frontline treatment of patients with ES-SCLC; this was followed by an approval in September 2019 by the European Commission.

In the international, randomized, placebo-controlled, double-blind, phase III IMpower133 trial 403 treatment-naïve patients with ES-SCLC were randomized to carboplatin/etoposide with either atezolizumab or placebo for four 21-day cycles followed by maintenance therapy with atezolizumab or placebo. Treatment continued until disease progression or loss of clinical benefit. Patients with treated asymptomatic brain metastases were eligible.

The approvals were both based on primary data from the IMpower133 trial, which showed a significant improvement in OS, as well as progression-free survival, compared with carboplatin/etoposide in this patient population.²

In the primary analysis, at a median follow-up of 13.9 months, the primary endpoint of median OS was 12.3 months in the atezolizumab plus carboplatin/etoposide arm compared with 10.3 months in the placebo plus carboplatin/etoposide arm (HR, 0.70; 95% CI, 0.54-0.91; P = .007).³ The median PFS, a coprimary endpoint, was 5.2 versus 4.3 months, respectively (HR, 0.77; 95% CI, 0.62-0.96; P = .02). The survival benefit was observed across all subgroups.

Longer follow-up of the data was presented at the 2019 ESMO Congress. At a median follow-up of 22.9 months, the median OS remained 12.3 months in patients randomized to atezolizumab and was 10.3 months for patients on placebo plus standard therapy (HR, 0.76; 95% CI, 0.60-0.95; P = .0154).⁴

At 18 months, 34% of patients were alive in the atezolizumab and carboplatin/etoposide arm compared with 21% in the placebo arm. Response rates were comparable between arms, with 60.2% and 64.4%, having complete or partial responses in the atezolizumab and chemotherapy-alone arms, respectively. The median duration of response was 4.2 and 3.9 months, respectively.

Additionally, a post hoc exploratory analysis was conducted for OS by PD-L1 expression in 34% (n = 137) of the intent-to-treat (ITT) population in whom PD-L1 expression was measured via the Ventana SP263 assay.

Tumor cells were negative for PD-L1 expression in 94.2% of the biomarker evaluable population compared with 49.6% of immune cells. In contrast, PD-L1 positivity on tumor cells was observed in only 5.8% of the patients, compared with 50.4% on immune cells. A total 1.5% and 20.4% of patients had high (≥5%) PD-L1 expression on immune cells and tumor cells, respectively.

The efficacy of atezolizumab on OS was comparable between the biomarker evaluable population and non-biomarker evaluable population. There was a numerical advantage favoring atezolizumab plus carboplatin/etoposide in patients with high PD-L1 expression compared with the ITT population, but only 29 patients had high PD-L1 expression.

Subsequent therapy was received by 54.7% of patients randomized to the atezolizumab combination and 61.9% of those assigned to placebo plus chemotherapy. The most frequently used subsequent class of therapy was non-anthracycline chemotherapy.

Regarding safety, there was no change in tolerability in the updated analysis. About two-thirds of patients in each arm had grade 3/4 adverse events (AEs) and 35.2% of those on the placebo arm and 38.9% of those on atezolizumab had serious AEs.

The incidence of immune-related AEs was higher with atezolizumab compared with chemotherapy alone (41.4% vs 24.5%). The most frequent immune-related AEs in the atezolizumab arm were rash (20.2%), hepatitis (7.6%), changes in thyroid function (18.2%), and infusion-related reactions (5.5%). There were no grade 5 immune-related AEs.

References

1. Atezolizumab with carboplatin and etoposide for untreated extensive-stage small-cell lung cancer [appraisal consultation document]. National Institute for Health and Care Excellence. Published December 31, 2019. bit.ly/37KteKK. Accessed January 6, 2020.
2. FDA approves Genentech’s Tecentriq in combination with chemotherapy for the initial treatment of adults with extensive-stage small cell lung cancer [news release]. South San Francisco, CA: Genentech (Roche); March 18, 2019. bit.ly/2Y5jVkw. Accessed March 19, 2019.
3. Horn L, Mansfield AS, Szcesna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220-2229.
4. Reck M, Liu SV, Mansfield AS, et al. IMpower133: updated overall survival (OS) analysis of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC). Ann Oncol. 2019;30(suppl_5):v710-v717. doi: 10.1093/annonc/mdz264.