IMpower010: Impact of type and extend of prior therapy on disease-free survival in atezolizumab–treated patients

Surgical resection followed by adjuvant chemotherapy is a standard of care in stage II-III non-small cell lung cancer (NSCLC). Time from surgery to adjuvant treatment as well as the type and extent of mediastinal staging remain topics of interest. Post-hoc analyses of the types and frequency of thoracic surgery prior to adjuvant atezolizumab in patients enrolled in the IMpower010 trial now explored the potential impact of these therapies on disease-free survival.

In stage II-III NSCLC, surgical resection followed by adjuvant chemotherapy is a standard of care. The phase III IMpower010 trial is evaluating atezolizumab versus best supportive care (BSC) after adjuvant chemotherapy in patients with completely resected NSCLC and, at the DFS interim analysis, met its primary endpoint. Adjuvant atezolizumab showed significant DFS benefit vs. BSC in the PD L1 TC ≥1% (per SP263) stage II-IIIA and the all-randomised stage II-IIIA populations while the statistical significance boundary for DFS was not crossed in the ITT (all-randomised stage IB-IIIA) population. OS data were still immature at the DFS interim analysis. Now, the potential impact of prior therapies, including surgery type, on DFS outcomes in patients receiving adjuvant atezolizumab or BSC in IMpower010 were explored.

The IMpower010 trial

IMpower010 enrolled 1,280 patients of which 1,269 patients received up to four 21-day cycles of adjuvant chemotherapy (cisplatin, partnered with either pemetrexed, docetaxel, gemcitabine or vinorelbine). In total, 1,005 of these patients were subsequently randomised (1:1) to sixteen cycles of atezolizumab (1,200 mg Q3W) or BSC. All eligible patients had completely resected (4-12 weeks prior to enrolment) Stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and had an ECOG performance status of 0-1. The primary endpoint of investigator-assessed DFS and secondary endpoint of overall survival (OS) were tested hierarchically: first DFS in the PD-L1 tumour cell (TC) ≥1% (SP263) subgroup with Stage II-IIIA disease, then DFS in all randomised patients with Stage II-IIIA disease, and finally DFS in the ITT population (Stage IB-IIIA). Only if the latter analysis was positive, the OS could be tested in the ITT population. Baseline patient characteristics were well balanced between all treatment arms.

Study results

The median age of the patients was 62 years and 67% of patients were male. Most patients had non-squamous histology (65.6%) and 12.2% of patients had stage IB disease. In total, 54.6% of patients had PD-L1 TC expression levels ≥1%. The most common type of surgery was lobectomy (78.1%); 15.9% had pneumonectomy and 5.0% had bilobectomy. Mediastinal lymph node dissection or sampling was performed in 80.7% and 18.0% of patients, respectively. Median (range) time from surgery to first atezolizumab treatment or BSC was 5.2 months (2.4-7.7) and 5.1 months (2.3-8.0) in the atezolizumab and BSC arms, respectively. A median of 4 (range, 1-4) adjuvant chemotherapy cycles were received for all regimens; 152 patients received cisplatin-docetaxel, 165 received cisplatin-gemcitabine, 303 received cisplatin-vinorelbine and 385 received cisplatin-pemetrexed.

Adjuvant atezolizumab demonstrated a statistically significant DFS benefit over BSC in the PD-L1 TC ≥1% Stage II-IIIA population (median DFS not evaluable vs. 35.3 months, HR[95%CI]: 0.66[0.50-0.88], p= 0.004). Furthermore, atezolizumab also reduced the risk of disease recurrence or death by 21% in the all-randomised population of patients with stage II-IIIA NSCLC, with a median DFS of 42.3 months  vs. 35.3 months with BSC (HR[95%CI]: 0.79[0.64-0.96], p= 0.02). In the ITT population (stage IB-IIIA NSCLC), the statistical significance boundary for DFS was not crossed for atezolizumab versus BSC. For these patients the median DFS was not estimable in the atezolizumab arm as compared to 37.2 months with BSC (HR[95%CI]: 0.81[0.67-0.99], p= 0.04).

Exploratory subgroup analysis in patients with PD-L1 TC ≥1% Stage II-IIIA (N= 476) revealed that DFS favoured atezolizumab across most disease stages, in patients with nodal involvement and across most surgery types and chemotherapy regimens. The same holds true for the all-randomised stage II-IIIA population (N= 882). In the ITT population, DFS was again favouring the atezolizumab arm but as statistical significance was not crossed yet, results still await the final DFS analysis.

Conclusion

At the DFS interim analysis of IMpower010, atezolizumab showed statistically significant DFS benefit vs. BSC in the PD-L1 TC≥1% stage II-IIIA and all-randomised stage II-IIIA populations. In this exploratory analysis, improved DFS was observed with adjuvant atezolizumab vs. BSC in the PD-L1 TC≥1% stage II-IIIA and all-randomised stage II-IIIA populations across most disease stages, in patients with nodal involvement, and across most surgery types and chemotherapy regimens.

Reference

Altorki N, Felip E, Zhou C, et al. IMpower010: Characterization of Stage IB-IIIA NSCLC Patients by Type and Extent of Therapy Prior to Adjuvant Atezolizumab. Presented at the 2021 World Conference on Lung Cancer; Abstract PL02.05.