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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Presentations: 2
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
P016 - The Optimal ALK inhibitor in Advanced ALK-Positive NSCLC Patients: An Indirect Comparison Between Brigatinib and Alectinib (ID 224)
00:00 - 00:00 | Author(s): H Zhou
Recent randomized phase III trials (ALTA-1L and ALEX) reported the robust efficacy of next-generation anaplastic lymphoma kinase (ALK) inhibitors (brigatinib and alectinib) for the first-line treatment of patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). However, there is no head-to-head comparison of brigatinib vs. alectinib. In this study, we aimed to explore the optimal choice of ALK inhibitors treatment for advanced ALK-Positive NSCLC.
We performed an indirect comparison of ALTA-1L and ALEX to compared therapeutic efficacy and adverse event (AE) between brigatinib and alectinib as the first-line treatment of advanced ALK-Positive NSCLC. The clinical outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and AE. Hazard ratio (HR, for PFS and OS) / risk ratio (RR, for ORR and AE) and its 95% confidence interval (CI) were extracted.
Brigatinib and alectinib had similar PFS (hazard ratio (HR) with 95% confidence interval, 1.14, 0.69-1.88; P=0.61) and OS (HR, 1.29, 0.58-2.85; P=0.53), while they had similar ORR, all cause AE and grade 3-5 AE. For patients with/without baseline CNS metastases, Brigatinib and alectinib still showed similar PFS.
Our study revealed that brigatinib and alectinib may be similar in terms of efficacy and safety for the first-line treatment of patients with ALK-positive NSCLC.
P025 - Which Is the Optimal Immunotherapy for Advanced Non-Squamous Non-Small-Cell Lung Cancer in Combination with Chemotherapy? (ID 222)
00:00 - 00:00 | Author(s): H Zhou
Two phase III randomized clinical trials (KEYNOTE-189 and IMpower132) reported that the addition of anti-programmed death (ligand) 1 (anti-PD-(L)1) antibodies to first-line platinum-based chemotherapy improve the therapeutic efficacy for advanced non-squamous non-small-cell lung cancer (NSCLC). However, there is no head-to-head comparison of pembrolizumab (anti-PD-1) plus chemotherapy vs. atezolizumab (anti-PD-L1) plus chemotherapy.
In terms of chemotherapy as the bridge, we performed an indirect comparison of KEYNOTE-189 and IMpower132 to compared therapeutic efficacy and adverse event (AE) between pembrolizumab (N=410) and atezolizumab (N=292) in combination with chemotherapy as the first-line treatment of advanced squamous NSCLC. Data of overall survival (OS) and progression-free survival (PFS) were extracted as hazard ratio (HR) and its 95% confidence interval (CI), while data of objective response rate (ORR) and AE were extracted as risk ratio (RR) and its 95% CI.
For overall patients, pembrolizumab had significantly superior OS (HR, 0.60, 0.43-0.86; P<0.01) and a significant increase of ORR (RR, 2.09, 1.24-3.52; P<0.01) than atezolizumab in combination with chemotherapy, while they had similar PFS (HR, 0.87, 0.66-1.14; P=0.31), all cause AE and grade 3-5 AE. For PD-L1 low/high patients, pembrolizumab and atezolizumab showed similar PFS. However, for PD-L1 negative patients, atezolizumab had significantly superior PFS (HR, 1.67, 1.01-2.74; P=0.04) than pembrolizumab. Table 1. Indirect comparison of pembrolizumab plus chemotherapy vs. atezolizumab plus chemotherapy for advanced non-squamous non-small-cell lung cancer. Item Statistical analysis HR / RRa (95%CI) P-value Overall OS 0.60 0.43 0.86 < 0.01 PFS 0.87 0.66 1.14 0.31 Overall ORR 2.09 1.24 3.52 < 0.01 All cause AE 2.35 0.16 33.64 0.53 Grade 3-5 AE 0.67 0.41 1.10 0.11 Subgroup (PFS) PD-L1 Highb,c 0.78 0.34 1.78 0.56 PD-L1 Lowd 0.69 0.40 1.17 0.17 PD-L1 Negativee 1.67 1.01 2.74 0.04 < 65 y 0.68 0.47 0.99 0.04 ?65 y 1.36 0.90 2.06 0.14 Male 1.03 0.72 1.47 0.86 Female 0.78 0.49 1.24 0.30 ECOG PS 0 0.88 0.56 1.37 0.56 ECOG PS 1 0.89 0.63 1.26 0.51 Smoker 0.89 0.66 1.18 0.41 Never smoker 0.88 0.38 2.05 0.76 Carboplatin 1.02 0.73 1.42 0.91 Cisplatin 0.68 0.41 1.11 0.12 Abbreviations: CI = confidence interval; HR = Hazard ratio; RR = Risk ratio; OS = overall survival; PFS = progression-free survival; ORR = objective response rate; AE = adverse event; PD-L1= programmed death ligand 1. ECOG PS = Eastern Cooperative Oncology Group (ECOG) Performance Status aHR is used for OS and PFS evaluation, RR is used for ORR and AE evaluation. bPD-L1 status available in 60% (344/578) and 93.8 % (578/616) of patients in IMpower 132 and KEYNOTE-189 respectively. cPD-L1 High is defined as TC3 or IC3 in IMpower132, TPS ?50% in KEYNOTE-189. dPD-L1 Low is defined as TC1/2 or IC1/2 in IMpower132, TPS ?1% and <50% in KEYNOTE-189. ePD-L1 Negative is defined as TC0 and IC0 in IMpower132, TPS <1% in KEYNOTE-189.
Our results revealed that anti-PD-1 antibody may have superior efficacy compared to anti-PD-L1 antibody for advanced non-squamous NSCLC patients in combination with chemotherapy as first-line treatment. But anti-PD-L1 antibody might be better for PD-L1 negative patients. Further studies are warranted to confirm this.