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OA05 - Treatment Advances in SCLC (ID 373)
- Event: WCLC 2016
- Type: Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
OA05.05 - Randomized Phase 2 Study: Alisertib (MLN8237) or Placebo + Paclitaxel as Second-Line Therapy for Small-Cell Lung Cancer (SCLC) (ID 4855)
14:20 - 15:50 | Author(s): T. Csoszi
Alisertib, an investigational selective Aurora A kinase inhibitor, showed single-agent antitumor activity in preclinical in vivo SCLC models and was synergistic with paclitaxel in this setting. We report the efficacy, quality of life (QoL), and safety from this study.
Patients ≥18 years with SCLC relapsed <180 days after standard first-line platinum-based chemotherapy were randomized 1:1 to alisertib 40 mg orally twice-daily on days 1–3, 8–10, 15–17 + paclitaxel 60 mg/m IV on days 1, 8, 15 (Arm A) or matched placebo + paclitaxel 80 mg/m (Arm B) in 28-day cycles. Patients were stratified using an interactive voice response system (IVRS) by type of relapse post-frontline platinum (sensitive vs resistant/refractory) and presence/absence of brain metastases at baseline. Protocol Amendment 2 corrected the definition for relapse per standard guidance; stratification factors were corrected accordingly. Primary endpoint was progression-free survival (PFS) per stratified log-rank test. QoL outcomes were assessed per EORTC QLQ-C30 and -LC13.
178 patients were randomized, 89/89 to Arm A/B (median age 62/62 years). Survival, response, QoL, and safety results are presented in the Table. The analysis of PFS using IVRS stratification favored Arm A, as did the analysis per corrected stratification factors. Mean EORTC QLQ-C30 QoL scores were similar between arms, as were mean change-from-baseline values at end of treatment (-5.7 in Arm A vs -4 in Arm B). Figure 1
Alisertib + paclitaxel shows favorable PFS over placebo + paclitaxel with both initial and updated IVRS stratification. A similar favorable trend was also observed for OS and ORR although not statistically significant. Comparable changes in QoL scores were observed from baseline in both arms. The alisertib + paclitaxel arm showed higher rates of AEs and discontinuation due to AEs. Updated survival analyses are pending.
PL04a - Plenary Session: Immune Checkpoint Inhibitors in Advanced NSCLC (ID 430)
- Event: WCLC 2016
- Type: Plenary
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
PL04a.01 - Health-Related Quality of Life for Pembrolizumab vs Chemotherapy in Advanced NSCLC with PD-L1 TPS ≥50%: Data from KEYNOTE-024 (Abstract under Embargo until December 7, 7:00 CET) (ID 7153)
08:45 - 09:40 | Author(s): T. Csoszi
In KEYNOTE-024 (NCT02142738), pembrolizumab provided superior progression-free survival (PFS) over platinum-based chemotherapy as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression on ≥50% of tumor cells (ie, PD-L1 tumor proportion score [TPS] ≥50%) and no sensitizing EGFR or ALK aberrations (HR 0.50, P < 0.001). Despite a 44% crossover rate from chemotherapy to pembrolizumab, pembrolizumab also significantly improved overall survival (OS) (HR 0.60, P = 0.005). Any-grade (73% vs 90%) and grade 3-5 (27% vs 53%) treatment-related adverse events were less frequent with pembrolizumab. Health-related quality of life (HRQoL) is an important consideration for anticancer therapy, particularly in the first-line setting. We present data from the prespecified exploratory patient-reported outcomes (PRO) analysis of KEYNOTE-024.
305 patients were randomized to pembrolizumab 200 mg Q3W or investigator-choice platinum-doublet chemotherapy plus optional pemetrexed maintenance therapy for nonsquamous disease. The EORTC QLQ-C30 and QLQ-LC13 were administered at cycles 1-3 and every 9 weeks thereafter. The key PRO end points were change from baseline to week 15 in the QLQ-C30 global health status/QoL score and time to deterioration in the QLQ-LC13 composite of cough, chest pain, and dyspnea. PROs were analyzed for all patients who received study treatment and completed ≥1 PRO instrument (n = 299).
Across treatment arms, PRO compliance was >90% at baseline and ~80% at week 15. Least squares (LS) mean (95% CI) change from baseline to week 15 in QLQ-C30 global health status/QoL score was 6.95 (3.29 to10.58) for pembrolizumab (n = 151) and –0.88 (–4.78 to 3.02) for chemotherapy (n = 148). The difference in LS means was 7.82 (95% CI 2.85-12.79; nominal 2-sided P = 0.002). The proportion of improved global health status/QoL score at week 15 was 40.0% for pembrolizumab and 26.5% for chemotherapy. Fewer patients in the pembrolizumab arm had deterioration in the QLQ-LC13 composite of cough, dyspnea, and chest pain (30% vs 39%), and time to deterioration was also prolonged with pembrolizumab (HR 0.66, 95% CI 0.44-0.97; nominal 2-sided P = 0.029).
Pembrolizumab was associated with a clinically meaningful improvement in HRQoL compared with platinum-based chemotherapy. Combined with the superior PFS and OS and manageable safety profile, these data suggest pembrolizumab may be a new standard of care for first-line treatment of PD-L1–expressing advanced NSCLC.