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Manuel Cobo Dols
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MA 03 - Chemotherapy (ID 651)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Jin-Hyoung Kang, W. Su
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 502
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MA 03.01 - Nab-Paclitaxel ± CC-486 as Second-Line Treatment of Advanced NSCLC: Results from the ABOUND.2L+ Study (ID 8676)
11:00 - 11:05 | Author(s): Manuel Cobo Dols
- Abstract
- Presentation
Background:
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.
Method:
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[2] d8, 15 + CC-486 200 mg qd d1-14 or nab-paclitaxel 100 mg/m[2] 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.
Result:
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[2] and 800 mg/m[2] 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.
Conclusion:
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. NCT02250326nab-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.
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MA 10 - Immunotherapy I (ID 664)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:S. Wang, Robert Pirker
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 303 + 304
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MA 10.02 - Nab-Paclitaxel + Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+ (ID 8682)
11:05 - 11:10 | Author(s): Manuel Cobo Dols
- Abstract
- Presentation
Background:
Chemotherapy may enhance immunotherapeutic effects by causing tumor antigen release, which primes the immune system to kill tumor cells. Early clinical data on nab-paclitaxel + carboplatin in combination with immune checkpoint inhibitors (ICI) demonstrated promising activity without compounding toxicities in patients with non-small cell lung cancer (NSCLC). ABOUND.2L+ evaluated nab-paclitaxel–based regimens in previously treated patients with advanced NSCLC. Here we report the efficacy and safety of nab-paclitaxel + durvalumab as second/third-line treatment.
Method:
Patients with advanced NSCLC were assigned to receive second/third-line (immunotherapy allowed in prior line, including platinum doublet combination) nab-paclitaxel 100 mg/m[2] on days 1 and 8 + durvalumab 1125 mg on day 15, in 21-day cycles, administered until unacceptable toxicity/progression per immune-related RECIST v1.1. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety.
Result:
Seventy-nine patients were enrolled. Median age was 63 years, 68% of patients were male, 23% had Eastern Cooperative Oncology Group performance status of 0, and 70% had nonsquamous NSCLC; 11% of patients received prior ICIs. Median PFS (Table) and OS were 4.5 (3.4-5.8) months and NE (7.3-NE). ORR was 27% (1 complete response) and DCR was 71%. Grade 3/4 treatment-emergent adverse events of special interest occurring in ≥ 5% of patients included neutropenia (6%) and dyspnea (5%); grade 3/4 peripheral neuropathy and anemia each occurred in 4% of patients. Median treatment duration was 24 weeks; median number of treatment cycles was 7. For nab-paclitaxel and durvalumab, median dose intensities were 59.05 mg/m[2]/week and 326.61 mg/week, respectively; median percentages of per-protocol dose were 88.58% and 87.10%.
Conclusion:
The combination of durvalumab with nab-paclitaxel demonstrated antitumor activity with manageable toxicity in the second/third-line setting. Further details will be presented. NCT02250326Nab-P Durva Median PFS (range), months Overall (n = 79) 4.5 (3.4-5.8) ICI pretreated (n = 9)[a] ICI naive (n = 69)[a] 6.9 (1.4-NE) 4.4 (3.0-5.7) Squamous (n = 23)[a] Nonsquamous (n = 55)[a] 5.9 (3.0-7.8) 4.2 (2.9-5.7) ICI, immune checkpoint inhibitor; NE, not estimable; PFS, progression-free survival. [a] Data pending for 1 patient.
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OA 17 - Immunotherapy II (ID 683)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yuichiro Ohe, Anne Tsao
- Coordinates: 10/18/2017, 14:30 - 16:15, Room 301 + 302
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OA 17.07 - Long-Term Survival in Atezolizumab-Treated Patients with 2L+ NSCLC from Ph III Randomized OAK Study (ID 8663)
15:35 - 15:45 | Author(s): Manuel Cobo Dols
- Abstract
- Presentation
Background:
Atezolizumab (anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. OAK, a Phase III study of atezolizumab vs docetaxel demonstrated superior OS of atezolizumab. The characteristics of the long-term survivors (LTS) in the OAK primary population (n = 850) are evaluated and describe the largest cohort of cancer immunotherapy-treated NSCLC LTS yet reported.
Method:
Patients received IV q3w atezolizumab (1200 mg) until PD / loss of clinical benefit or docetaxel (75 mg/m[2]) until PD / unacceptable toxicity. No crossover was allowed. LTS were defined as patients with OS ≥ 24 months and non-LTS as those who died within 24 months of randomization. Patients with OS censored prior to 24 months were not included. Data cutoff, January 23, 2017.
Result:
A higher 2-year survival rate was observed for the atezolizumab-arm (31%) vs docetaxel-arm (21%). After a minimum follow-up of 26 months, there were 119 LTS vs 279 non-LTS in the atezolizumab-arm and 77 LTS vs 299 non-LTS in the docetaxel-arm. Characteristics of atezolizumab-arm LTS and non-LTS are shown (Table). Atezolizumab-arm LTS were enriched for non-squamous histology and high PD-L1–expressing tumors, but also included low/no PD-L1–expressing tumors (40.3%). Atezolizumab-arm LTS had higher ORR (39.5%) than non-LTS (5.0%) but included LTS subjects with PD. 52.9% atezolizumab-arm vs 71.4% docetaxel-arm LTS received anti-cancer non-protocol therapy (NPT) after discontinuation of protocol-defined therapy. 51.9% of docetaxel-arm LTS vs 12.7% non-LTS received non-protocol immunotherapy. Median treatment exposure in atezolizumab-arm LTS was 18.0 months. Atezolizumab-arm LTS had a comparable safety profile to all atezolizumab-treated population.
Conclusion:
Atezolizumab provides superior 2-year OS benefit vs docetaxel and is well tolerated. The majority of docetaxel-arm LTS received a checkpoint inhibitor as NPT. Atezolizumab LTS appeared to have favorable prognostic factors, including non-squamous histology, but notably were not limited to patients with RECIST v1.1 response or with PD-L1 expression.Table. Characteristics of Atezolizumab-Arm Long-Term Survivors (LTS) vs Non-Long Term Survivors (Non-LTS) Atezolizumab LTS (n = 119) n (%) Atezolizumab Non-LTS (n = 279) n (%) Sex Male 61 (51.3) 183 (65.6) Female 58 (48.7) 96 (34.4) Tobacco use history Never smoker 29 (24.4) 47 (16.8) Current/previous smoker 90 (75.6) 232 (83.2) Histology Non-squamous 101 (84.9) 195 (69.9) Squamous 18 (15.1) 84 (30.1) No. of prior therapies, 1 89 (74.8) 209 (74.9) ECOG performance status at baseline 0 60 (50.4) 89 (31.9) 1 59 (49.6) 190 (68.1) EGFR mutation status, positive 11 (9.2) 26 (9.3) PD-L1 IHC subgroup TC3 or IC3 28 (23.5) 39 (14.0) TC1/2/3 or IC1/2/3 71 (59.7) 156 (55.9) TC0 and IC0 48 (40.3) 119 (42.7) Best overall response Complete response 5 (4.2) 0 (0) Partial response 42 (35.3) 14 (5.0) Stable disease 47 (39.5) 97 (34.8) Progressive disease 25 (21.0) 142 (50.9) IC, tumor-infiltrating immune cell; TC, tumor cell. TC3 or IC3 = PD-L1 ≥ 50% TC or 10% IC; TC1/2/3 or IC1/2/3 = PD-L1 ≥ 1% on TC or IC; TC0 and IC0 = PD-L1 < 1% on TC and IC. NCT02008227.
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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)
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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)
08:40 - 08:50 | Author(s): Manuel Cobo Dols
- Abstract
- Presentation
Background:
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.
Method:
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.
Result:
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.
Conclusion:
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)
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