Atezolizumab Regimen Improves OS After TKI Failure in EGFR+ NSCLC

Martin Reck, MD, PhD

Atezolizumab (Tecentriq) plus bevacizumab (Avastin), carboplatin, and paclitaxel (ABCP) has emerged as a potential new standard of care for patients with EGFR-positive metastatic nonsquamous non—small cell lung cancer (NSCLC) who have failed on TKI treatment, according to an exploratory analysis from the phase III IMpower150 trial presented at the 2019 European Lung Cancer Congress (ELCC).¹

The data, which were also recently published in Lancet Respiratory Medicine,² showed that ABCP reduced the risk of death by 39% compared with a regimen of bevacizumab, carboplatin, and paclitaxel (BCP). The median OS was not yet reached with ABCP compared with 18.7 months (95% CI, 13.4-NE) with BCP (HR, 0.61; 95% CI, 0.29-1.28).

“IMpower150 is the first phase III immunotherapy-based combination study to demonstrate a statistically significant and clinically meaningful improvement in OS in patients with metastatic nonsquamous NSCLC and EGFR mutation, providing a potential new standard of care for these patients,” said Martin Reck MD, PhD, Department of Thoracic Oncology at the Lung Clinic Grosshansdorf in Grosshansdorf, Germany.

The IMpower150 trial overall enrolled 1202 patients who were randomized equally to receive atezolizumab at 1200 mg plus carboplatin AUC 6 plus paclitaxel at 200 mg/m² (arm A); atezolizumab plus bevacizumab at 15 mg/kg plus chemotherapy (arm B); or bevacizumab plus chemotherapy (arm C). The agents were administered by IV every 3 weeks for 4 or 6 cycles per investigator decision, followed by maintenance with atezolizumab plus bevacizumab or single-agent atezolizumab or bevacizumab, respectively. The primary endpoints were OS and investigatory-assessed progression-free survival in the ITT—wild-type population.

“The trial explored these combinations because atezolizumab inhibits PD-L1 to restore anticancer immunity and may be enhanced through bevacizumab’s inhibition of VEGF immunosuppression and by promoting T-cell tumor infiltration, while the chemotherapy of carboplatin plus paclitaxel may induce immune responses,” Reck said while explaining the study rationale.

Reck presented findings at the 2019 ELCC from the IMpower150 exploratory analyses, which included patients with EGFR mutations (EGFR-mt), patients with sensitizing EGFR-mt (EGFR-mts), and EGFR-mt patients with prior TKI therapy. The exploratory analyses occurred at ≥20 months’ follow-up and included 79 patients overall (EGFR-mt population), of whom 58 (73%) comprised the EGFR-mts subgroup, and 50 (63%) comprised the subgroup who had received prior TKI therapy. The baseline characteristics of the EGFR-mt patients across treatment arms were generally comparable to those in the ITT population.

For the comparison of OS with ABCP (Arm B) versus BCP (Arm C), all HRs favored the quadruplet across the 3 subgroups. In EGFR-mt patients, the median OS was not reached in arm B versus 18.7 months in arm C (HR, 0.61; 95% CI, 0.29-1.28); in EGFR-mts patients, the median OS was not reached versus 17.5 months, respectively (HR, 0.31; 95% CI, 0.11-0.83); and in patients receiving prior TKIs, the median OS was not reached versus 17.5 months (HR, 0.39; 95% CI, 0.14-1.07).

The objective response rates in EGFR-mt patients were 36%, 71%, and 42%, and the median duration of response was 5.6 months (range, 2.6-15.2), 11.1 months (range, 2.8-18.0), and 4.7 months (range, 2.6-13.5) in arms A, B, and C, respectively.

Adverse events (AEs) included reporting of serious AEs and immunological AEs, which were similar between the treatment arms. In the EGFR-mt patients, the safety analysis comprised 44 patients in arm A, 33 patients in arm B, and 44 patients in arm C. Treatment-related AEs (TRAEs) occurred in 89%, 100%, and 96% of patients in arms A, B, and C, respectively; grade 3/4 TRAEs were reported in 57%, 64%, and 57% of patients in the respective groups. One grade 5 TRAE occurred in arm C.

Immune-related AEs were rash in 36%, 30%, and 11% of patients and hypothyroidism in 2%, 18%, and 2% of patients in arms A, B, and C, respectively.

“Adding atezolizumab to standard-of-care bevacizumab and chemotherapy provided a survival benefit in EGFR-mt patients who have failed previous TKIs; this regimen may represent a new treatment option for this patient population.”

References

1. Reck M, Jotte R, Mok TSK, et al. IMpower150: an exploratory analysis of efficacy outcomes in patients with EGFR mutations. Presented at: 2019 European Lung Cancer Congress; April 11 to 13, 2019; Geneva, Switzerland. Abstract 104O.
2. Reck M, Mok TSK, Nishio M et al. Atezolizumab plus bevacizumab and chemotherapy in non-small cell lung cancer (IMpower150): key subgroup analysis of patients with EGFR mutations or liver metastasis in a randomised, open label phase 3 trial. Lancet Respir Med. 2019 Mar 25. pii: S2213-2600(19)30084-0. doi: 10.1016/S2213-2600(19)30084-0.

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