IMpower010 Interim OS Findings ‘Support’ Adjuvant Atezolizumab Benefit–Risk Profile

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: The first prespecified interim overall survival (OS) findings from the IMpower010 trial add to evidence for the use of atezolizumab after adjuvant platinum-based chemotherapy in patients with completely resected stage II–IIIA non-small-cell lung cancer (NSCLC) that is positive for PD-L1 expression.

As presented at the IASLC World Conference on Lung Cancer 2022 in Vienna, Austria, the study recruited 1005 patients with completely resected IB–IIIA NSCLC who were randomly assigned to receive adjuvant chemotherapy followed by atezolizumab 1200 mg every 3 weeks for up to 1 year or best supportive care (BSC).

After median follow-up of 46 months, the trial show a trend towards improved OS with atezolizumab versus BSC but only among the subgroup of patients with stage II–IIIA disease and PD-L1 tumour cell (TC) expression of 1% or higher.

The data are yet to mature, explained presenting author Enriqueta Felip, from Vall d’Hebron University Hospital in Barcelona, Spain, and median OS was unreached for both the 248 atezolizumab-treated patients and the 228 controls, giving a nonsignificant hazard ratio (HR) of 0.71.

At 36 months, 82.1% of the atezolizumab arm of this subgroup were alive, as were 78.9% of the BSC arm, and the corresponding OS rates after 60 months were 76.8% and 67.5%.

Median OS was also unreached, after a median 45 months of follow-up, among the atezolizumab and BSC treatment arms for the other two primary populations of randomised patients with stage II–IIIA disease (n=882) and the intention-to-treat population of patients with stage IB–IIIA disease (n=1005), but in these analyses there was no separation of the OS curves.

Further analysis of OS among patients with stage II–IIIA disease and a PD-L1 TC of at least 1% indicated benefit with atezolizumab for most subgroups including by age, sex, tumour stage and histology. Although patients given cisplatin plus gemcitabine seemed to have a poorer outcome when compared with those given other regimens, the presenter noted that there were only 75 patients in this group.

When OS was assessed by biomarker status among patients with stage II–IIIA disease, there was a “clinically meaningful OS trend in favour of atezolizumab” among those with a PD-L1 TC of 50% or higher, delegates were told.

After excluding patients with EGFR or ALK alterations, the median OS was unreached in both the atezolizumab and control arms among this subgroup of patients and the HR was 0.42, and at 60 months, the OS rates were a respective 84.8% versus 67.5%, the presenter said.

The IMpower010 investigators previously showed a significant improvement in disease-free survival (DFS) with adjuvant atezolizumab versus BSC, leading to approval of the agent in patients with a PD-L1 TC of at least 50% in Europe and in those with a TC of at least 1% in the USA, China and Japan.

Enriqueta Felip said that the “overall safety profile was consistent” with the earlier analysis and that the additional 13 months of follow-up had revealed “no new or unexpected safety signals.”

Grade 3 or 4 treatment-related adverse events occurred in 10.7% of patients given atezolizumab versus none of the controls, with adverse events leading to treatment interruption or withdrawal in 28.7% and 18.2% of the atezolizumab arm, respectively, and none of the controls.

“These data support the previously reported positive benefit-risk profile of adjuvant atezolizumab in PD-L1+ resected NSCLC and contribute to evidence supporting standard of care use”, the presenter concluded.

“IMpower010 will continue to the final DFS analysis, with further OS follow-up and analyses.”

Discussing the results at the session, Benjamin Besse, from Gustave Roussy in Villejuif, France, noted that the OS curves for PD-L1-positive patients with stage II–IIIA disease in the IMPower010 trial continued to separate over follow-up, which is “a very good sign”.

Reviewing the available trial results for the use of adjuvant and neoadjuvant chemotherapy and PD-L1 inhibitors in NSCLC at different stages and treatment lines, he stated that “we have enough evidence to use adjuvant immunotherapy in stage II and IIIA resected NSCLC”.

However, he cautioned against asking “too much” from subgroup analyses, and encouraged the audience to “just generate hypotheses.”

Finally, Benjamin Besse postulated that “minimal residual disease is a key tool to build de-escalation trials” for these “very expensive drugs”.

Reference

PL03.09: Felip E, Altorki N, Vallieres E et al. IMpower010: Overall survival interim analysis of a phase III study of atezolizumab vs best supportive care in resected NSCLC. IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August.