Start Your Search
S. Ponce Aix
MA 03 - Chemotherapy (ID 651)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
MA 03.01 - Nab-Paclitaxel ± CC-486 as Second-Line Treatment of Advanced NSCLC: Results from the ABOUND.2L+ Study (ID 8676)
11:00 - 12:30 | Author(s): S. Ponce Aix
CC-486 (oral azacitidine) is an epigenetic modifier with potential effect as a priming agent for chemotherapy in patients with NSCLC. Outcomes of nab-paclitaxel+CC-486 vs nab-paclitaxel as second-line treatment of advanced NSCLC are reported.
Patients with advanced nonsquamous NSCLC and no more than 1 prior chemotherapy line (including platinum doublet combination) were randomized (1:1) to nab-paclitaxel 100 mg/m d8, 15 + CC-486 200 mg qd d1-14 or nab-paclitaxel 100 mg/m d1, 8, both administered q3w until progressive disease/unacceptable toxicity. Primary endpoint was PFS. Secondary endpoints: DCR, ORR, OS, and safety. QoL, an exploratory endpoint, was assessed on d1 of each cycle.
The nab-paclitaxel+CC-486 arm was discontinued in October 2016 due to demonstrated futility vs nab-paclitaxel monotherapy upon completion of a protocol-specified interim analysis. Overall, 161 patients were randomized (nab-paclitaxel+CC-486, 81; nab-paclitaxel, 80). Baseline characteristics were balanced between arms. The median number of cycles was 4 for each arm, and the median nab-paclitaxel cumulative dose was 600 mg/m and 800 mg/m in the nab-paclitaxel+CC-486 and nab-paclitaxel arms, respectively. Rates of grade 3/4 (G3/4) treatment-emergent AEs were 59.5% and 54.4% for the combination and monotherapy arms, respectively. The most frequent hematologic G3/4 AEs were neutropenia (16.5% vs 10.1%) and anemia (1.3% vs 7.6%). G3/4 peripheral neuropathy was reported in 2.5% and 7.6% of patients, respectively. The addition of CC-486 to nab-paclitaxel did not improve ORR, DCR, PFS, or OS (Table). When assessed by Lung Cancer Symptom Scale, nab-paclitaxel monotherapy was associated with improvement in the global QoL, average symptom burden index, and lung cancer symptoms except for hemoptysis.
The addition of CC-486 to nab-paclitaxel did not clinically benefit patients with previously treated NSCLC. However, single-agent nab-paclitaxel appears to be a promising therapy based on safety, efficacy, and QoL data. Updated efficacy and safety data will be presented. NCT02250326
nab-Paclitaxel + CC-486 n = 81 nab-Paclitaxel n = 80 Median PFS, months 3.2 4.2 HR (95% CI) 1.3 (0.9 - 2.0) 1-year PFS, % 4.1 18.3 Median OS, months 8.4 12.7 HR (95% CI) 1.4 (0.88 - 2.31) 1-year OS, % 39.2 54.3 ORR, n (%)[a] 11 (13.6) 11 (13.8) Response rate ratio (95% CI) 0.99 (0.45 - 2.15) CR PR SD PD DCR (≥ SD) 0 11 (13.6) 41 (50.6) 22 (27.2) 52 (64.2) 0 11 (13.8) 43 (53.8) 19 (23.8) 54 (67.5) CR, complete response; DCR, disease control rate; HR, hazard ratio; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease. [a] Response rate was based on the intent-to-treat population; however, 14 patients did not have a response assessment.
PL 02 - Presidential Symposium including Top 3 Abstracts and James Cox Lectureship Award Presentation (ID 585)
- Event: WCLC 2017
- Type: Plenary Session
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:Hisao Asamura, Keunchil Park
- Coordinates: 10/17/2017, 08:15 - 09:45, Plenary Hall (Exhibit Hall D)
PL 02.04 - SCAT Ph III Trial: Adjuvant CT Based on BRCA1 Levels in NSCLC N+ Resected Patients. Final Survival Results a Spanish Lung Cancer Group Trial (ID 9523)
08:15 - 09:45 | Author(s): S. Ponce Aix
Postop platinum-based CT is considered standard of care in resected NSCLC with lymph node involvement. BRCA1 and BRCA2 are important DNA repair factors primarily involved in the repair of double strand DNA breaks. BRCA-1 functions may act as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency enhances Cis resistance and loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons.
SCAT randomized phase III multicenter trial tests individualized optimal CT based on expression of BRCA1. After surgery patients (p) with St II and Iii NCSLC were random 1:3 to control arm (3 cycles Cis-Docetaxel) or to experimental arm with treatment assigned according BRCA1 expression levels (low levels: Cis-Gemcitabine; intermediate levels: Cis-Doc; high levels: Docetaxel alone). Stratification factors: N1 vs N2; age < or > 65 y; non-Squamous vs Squamous (Sq) histology; lobectomy vs pneumonectomy). Planned PORT in N2. Primary end-point OS. Secondary end-points DFS, toxicity profile (CTCAE v 3.0) /compliance, recurrence pattern. Statistical hypothesis: 5y survival rate control group (45%) could be increase 20% in experimental arm.
From June/2007 to May/2013, a total of 591 p were screened and 500 of them were randomized in the study, 108 in control arm, 392 in experimental arm. In experimental arm 110 p received Cis-Gem, 127 Cis-Doc and 110 Doc alone. There were no significant differences between arm for known prognostic factors: Median age 64 y; 79% males, 21% females; 43% Sq, 49% Adenoca, 8% others; 57% former smokers, 32% current smokers, 11% never smokers; pneumonectomy 26%; N1 58%, N2 48%. Median tumor size 4.4 cm (0.8-15.5 cm). Median mRNA BRCA1 levels 15.78 (0.73-132). Mean BRCA1 levels 6.95 in Adenoca vs 20.29 in Sq (p<0.001). Compliance of CT was better in experimental arm with less dose-reductions and without differences according extent of surgery. CT compliance was lower in patients older 70 y. Median PFS: 38.7 m (control), 32.2 m Cis-Gem, 34.3 m Cis-Doc and 41 m Doc. At 5 years, event-free rate is 54% in control arm and 56% in experimental arm and median OS 73.3 m (control) vs 77.5 m (exp) (p=0.75). In experimental arm: Docetaxel alone 80.2 m, Cis-Doc 80.5 m and Cis-Gem 74 m.
Higher survival than expected in patients with lymph node involvement. No significant difference in survival achieved with the experimental arm. In case of high levels BRCA CT treatment without cisplatin is not detrimental. (Eudract:2007-000067-15; NCTgov: 00478699)