PL02.05 IMpower010: Characterization of Stage IB-IIIA NSCLC Patients by Type and Extent of Therapy Prior to Adjuvant Atezolizumab

Abstract

Surgical resection followed by adjuvant chemotherapy is a standard of care in stage II-III NSCLC. Time from surgery to adjuvant treatment as well as the type and extent of mediastinal staging remain topics of interest. At this interim analysis, the Phase III IMpower010 trial met its primary endpoint, showing significant disease-free survival (DFS) improvement with atezolizumab vs best supportive care (BSC) after adjuvant chemotherapy in patients with PD-L1 TC≥1% stage II-IIIA NSCLC and all randomized patients with stage II-IIIA NSCLC; the significance boundary for DFS was not crossed in the ITT population (stage IB-IIIA NSCLC). We investigated therapies prior to adjuvant atezolizumab, including surgery type, and their potential impact on DFS. IMpower010 enrolled patients with completely resected stage IB (tumors ≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0/1. Complete resection must have been performed 4-12 weeks prior to enrollment. Patients (N=1280) received up to four 21-day cycles of cisplatin-based chemotherapy, and 1005 were subsequently randomized 1:1 to atezolizumab 1200 mg Q3W (16 cycles or until disease recurrence or unacceptable toxicity) or BSC. The primary endpoint of investigator-assessed DFS was tested hierarchically in the PD-L1 TC≥1% (SP263) stage II-IIIA population, all-randomized stage II-IIIA population, and ITT population (stage IB-IIIA). Exploratory analyses of the types and frequency of thoracic surgery in patients from this global registration trial will be reported. The type of surgery, time from surgery to adjuvant treatment, including initiation of both chemotherapy and atezolizumab, and type and extent of mediastinal staging will be examined for any impact on the DFS endpoint. DFS by disease stage and nodal status (N0 vs N1 vs N2) will be presented. The ITT population included 507 (atezolizumab) and 498 (BSC) patients; median follow-up was 32.2 months (data cutoff: 21 Jan 2021). The most common 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 chemotherapy treatment was 1.8 mo (0.9-5.3) and 1.7 mo (0.8-5.2) 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. Median (range) time from surgery to first atezolizumab treatment or BSC was 5.2 mo (2.4-7.7) and 5.1 mo (2.3-8.0), respectively. DFS by disease and prior treatment characteristics in the PD-L1 TC≥1% stage II-IIIA, all-randomized stage II-IIIA and ITT populations is shown in the Table. In these exploratory analyses, most patients had lobectomy, lymph node dissection and 4 cycles of adjuvant chemotherapy. Median time from surgery to start of randomized treatment was similar between arms. Benefit was seen across disease stages (stage II-IIIA sub-populations), including patients with nodal involvement (N1 and N2). Additional details will be presented.Tabled 1SubgroupPD-L1 TC≥1% stage II-IIIAAll randomized stage II-IIIAITT (stage IB-IIIA)NmDFS (atezo vs BSC), moHRa (95% CI)NmDFS (atezo vs BSC), moHRa (95% CI)NmDFS (atezo vs BSC), moHRa (95% CI)All patients476NE vs 35.30.66 (0.50, 0.88)88242.3 vs 35.30.79 (0.64, 0.96)1005NE vs 37.20.81 (0.67, 0.99)bDisease stageStage IB––––––123NE vs NE1.01 (0.48, 2.13)Stage IIA161NE vs NE0.73 (0.43, 1.24)295NE vs NE0.68 (0.46, 1.00)295NE vs NE0.68 (0.46, 1.00)Stage IIB83NE vs NE0.77 (0.35, 1.69)17437.1 vs 46.40.88 (0.54, 1.42)17437.1 vs 46.40.88 (0.54, 1.42)Stage IIIA23242.3 vs 26.70.62 (0.42, 0.90)41332.3 vs 29.70.81 (0.61, 1.06)41332.3 vs 29.70.81 (0.61, 1.06)Regional lymph node status (pN)N010636.7 vs NE0.88 (0.45, 1.74)229NE vs 46.40.88 (0.57, 1.35)352NE vs NE0.93 (0.64, 1.36)N+370NE vs 31.40.62 (0.46, 0.85)65342.3 vs 31.40.76 (0.60, 0.96)65342.3 vs 31.40.76 (0.60, 0.96)N1194NE vs NE0.59 (0.36, 0.97)348NE vs 36.00.67 (0.47, 0.95)348NE vs 36.00.67 (0.47, 0.95)N217632.3 vs 21.30.66 (0.44, 0.99)30530.2 vs 24.10.83 (0.61, 1.13)30530.2 vs 24.10.83 (0.61, 1.13)Type of surgerycLobectomy359NE vs 33.40.63 (0.45, 0.87)67542.3 vs 32.00.77 (0.61, 0.97)785NE vs 36.00.78 (0.62, 0.97)Bilobectomy2436.7 vs NE0.78 (0.18, 3.33)4736.7 vs NE1.02 (0.35, 2.98)5036.7 vs NE1.14 (0.39, 3.34)Pneumonectomy8536.1 vs NE0.83 (0.43, 1.58)15036.1 vs 42.10.91 (0.56, 1.47)16036.1 vs 42.10.98 (0.61, 1.57)Chemotherapy regimenCisplatin-docetaxel7136.1 vs 18.00.60 (0.30, 1.23)12436.1 vs 37.30.72 (0.42, 1.23)15236.1 vs 42.10.74 (0.45, 1.23)Cisplatin-gemcitabine7536.1 vs NE1.14 (0.50, 2.61)13836.1 vs 46.40.94 (0.56, 1.57)16536.7 vs 46.41.03 (0.62, 1.70)Cisplatin-vinorelbine161NE vs 34.20.55 (0.33, 0.92)271NE vs 37.00.67 (0.46, 0.99)303NE vs 37.00.63 (0.43, 0.91)Cisplatin-pemetrexed169NE vs 31.40.66 (0.42, 1.06)34942.3 vs 31.40.84 (0.61, 1.16)38542.3 vs 36.00.91 (0.67, 1.24)NCT02486718. mDFS, median disease-free survival; NE, not estimable.a Stratified for all patients; unstratified for all other subgroups.b At the time of this analysis (data cutoff 21 Jan 2021), DFS did not cross the significance boundary in the ITT population.c Subgroups with <10 patients are not shown. 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