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Atezolizumab Plus Standard Chemotherapy Improves Progression-Free Survival in Stage IV NSCLC


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The combination of atezolizumab (Tecentriq), a programmed cell death ligand 1 (PD-L1) inhibitor, plus carboplatin or cisplatin and pemetrexed (Alimta) as first-line therapy followed by pemetrexed plus atezolizumab maintenance therapy improved progression-free survival in patients with stage IV nonsquamous non–small cell lung cancer (NSCLC), according to an interim analysis of the phase III IMpower132 study. The atezolizumab plus chemotherapy combination improved progression-free survival by 40% in all patients compared with the control arm (carboplatin or cisplatin plus pemetrexed followed by pemetrexed for maintenance therapy).

Vassiliki A. Papadimitrakopoulou, MD

Vassiliki A. Papadimitrakopoulou, MD

“The combination of immunotherapy and chemotherapy has demonstrated a benefit in the first-line treatment of NSCLC. The phase III study met its primary endpoint,” stated lead author Vassiliki A. Papadimitrakopoulou,MD, Chief of the Section of Thoracic Oncology at MD Anderson Cancer Center, Houston. “The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone. This combination offers a valuable treatment option that restores tumor-specific T-cell immunity, prolonging survival for patients with stage IV nonsquamous NSCLC.” Dr. Papadimitrakopoulou presented these findings at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto.1

“The overall survival data showed numerical improvement for combination therapy,” she added. Longer follow-up is needed to establish a survival benefit.

Study Details

A global phase III trial, IMpower132 enrolled 578 patients with stage IV nonsquamous NSCLC without EGFR mutations or ALK rearrangements and randomly assigned them 1:1 to the investigational arm (containing atezolizumab) or the control arm (no atezolizumab). In the investigational arm, patients received 4 to 6 cycles of atezolizumab at 1,200 mg plus carboplatin or cisplatin plus pemetrexed, followed by maintenance therapy with pemetrexed plus atezolizumab. The control arm received four cycles of carboplatin/pemetrexed or cisplatin/pemetrexed followed by pemetrexed maintenance therapy. Maintenance therapy was continued until disease progression or toxicity.

The addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone.
— Vassiliki A. Papadimitrakopoulou, MD

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Collection of biomarker tissue was not mandatory in the trial, but tissue was available for PD-L1 analysis in 60% of participants. Baseline demographics were well balanced in the two study arms. About 50% were aged 65 and older, and about two-thirds were male; 12% were never-smokers, 12% had liver metastases, and PD-L1 expression was similar in both arms of the trial. A high PD-L1 expression was found in 14.2% of the investigational arm and 11.9% of the control arm.

At a median follow-up of 14.8 months (minimum, 11.7 months), the median progression-free survival was 7.6 months in the investigational arm vs 5.2 months in the control arm for all patients, reducing the risk of disease progression by 40% (P < .0001), according to investigator assessment. All subgroups had a preferential progression-free survival benefit from the atezolizumab-containing arm, including women (49% improvement), Asian patients (58% improvement), never-smokers (51% improvement), current and former smokers (39% improvement), and patients without liver metastases (44% improvement).

PD-L1 Results

Sixty percent of patients were evaluable for PD-L1 status. A benefit with the addition of atezolizumab was observed across all PD-L1 subgroups, although it was consistently greater for patients with higher expression of PD-L1.

In the PD-L1–high group, 12-month progression-free survival was 46%, and median progression-free survival was 10.8 months. In PD-

IMMUNOTHERAPY COMBINATION IN STAGE IV NSCLC

  • The combination of a PD-L1 inhibitor plus standard chemotherapy improves progression-free survival over standard chemotherapy alone.
  • The combination benefited all PD-L1 subgroups.
  • Survival was numerically better with immunotherapy plus chemotherapy, but longer follow-up is needed.

L1–low patients, 12-month progression-free survival was 27%, and median progression-free survival was 6.2 months. PD-L1–negative patients had a 12-month progression-free survival of 35% and a median progression-free survival of 8.5 months.

In this interim overall survival analysis, the investigational arm was numerically superior compared with the control arm, with a 4.5-month improvement in survival: the median overall survival was 13.6 months in the atezolizumab-containing arm vs 18.1 months in the control arm. At the time of the analysis, this difference was not statistically significant. The 12-month survival rate was 59.6% for the combination arm and 55.4% for the control arm. Further follow-up is needed to demonstrate a mature survival benefit.

Toxicity

Dr. Papadimitrakopoulou said there were no new safety signals to emerge in the course of the trial. The rate of grade 3 or 4 treatment-related adverse events was higher in the investigational arm: grade 3 events occurred in 54% vs 39% in the control arm, and grade 4 events occurred in 33% vs 16%, respectively.

OF NOTE

In the phase III IMpower 132 trial, patients were randomly assigned to:

  • The investigational arm of atezolizumab plus carboplatin or cisplatin and pemetrexed followed by maintenance with pemetrexed and atezolizumab, or
  • The control arm of carboplatin or cisplatin plus pemetrexed followed by maintenance therapy with pemetrexed.

There was an imbalance between the two arms in subsequent immunotherapy; 52% in the control group subsequently received checkpoint inhibitor therapy, compared with 37% in the investigational arm.

As expected, she continued, the adverse events of interest (ie, related to checkpoint inhibitor therapy) were higher in the atezolizumab-containing arm. Pneumonitis occurred in 2% vs 1%, respectively. Hepatitis occurred in 2% vs 0%, respectively.

Updates with further follow-up will be presented in 2019, she said. ■

DISCLOSURE: Dr. Papadimitrakopoulou is an advisory board member for Genentech/Hoffmann-La Roche and has received institutional research funding from Hoffmann-La Roche.

REFERENCE

1. Papadimitrakopoulou V, Cobo M, Bordoni R, et al: Impower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC. 2018 World Conference on Lung Cancer. Abstract OA05.07. Presented September 24, 2018.


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