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Mariano Provencio
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MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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MA02.03 - ASTRIS: A Real World Treatment Study of Osimertinib in Patients with EGFR T790M-Positive NSCLC (ID 12972)
10:40 - 10:45 | Author(s): Mariano Provencio
- Abstract
- Presentation
Background
Osimertinib is a third-generation, CNS-active EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitizing and EGFR T790M resistance mutations. We report results from a second planned protocol, optimal interim analysis of the ongoing ASTRIS study (NCT02474355).
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible patients receive osimertinib 80 mg once daily. Inclusion criteria: stage IIIB/IV T790M-positive non-small cell lung cancer (NSCLC); T790M status confirmed locally by validated test, not restricted by sample type; prior EGFR-TKI therapy received; WHO performance status (PS) 0−2; acceptable organ and bone marrow function and no history of interstitial lung disease (ILD) or QTc prolongation. Asymptomatic, stable CNS metastases are permitted. The primary efficacy outcome is overall survival (OS).
4c3880bb027f159e801041b1021e88e8 Result
From Sept 18, 2015, first patient in, to Oct 20 2017 data cut-off (DCO), 3014 patients were enrolled across 16 countries and received ≥1 dose of osimertinib (full analysis set [FAS]): median follow-up 7.9 months (range <1−24), median age 62 yrs (27–92), 64% female, 69% Asian, 30% White, 11% WHO PS 2, 45% prior chemotherapy, 34% prior radiotherapy. All patients had T790M-positive status, identified from tissue in 1610 patients (53%), plasma ctDNA in 1241 patients (41%) and from other sources in 162 patients (5%). At DCO, 1276 patients (42%) had discontinued treatment (1738 [58%] ongoing); median duration of exposure 7.4 months (<1–25); 1289 patients (43%) had a progression-free survival (PFS) event, 1276 (42%) had a time to treatment discontinuation (TTD) event, and 593 (20%) had died. In patients evaluable for response, the investigator-assessed clinical response rate was 56.6% (1625/2872; 95% confidence interval [CI] 54.7, 58.4). In the FAS, estimated median PFS was 11.0 months (95% CI 10.6, 11.1), median TTD was 12.6 months (95% CI 12.2, 13.7), and median OS was not reached (OS at 12 months was 75.8% (95% CI 73.7, 77.8). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 321 patients (11%) and 147 patients (5%), respectively. Serious AEs were reported in 505 patients (17%). ILD/pneumonitis-like events were reported in 41 patients (1%), and QTc prolongation in 48 patients (2%).
8eea62084ca7e541d918e823422bd82e Conclusion
ASTRIS, the largest reported study of osimertinib in T790M-positive NSCLC, demonstrates clinical activity similar to that observed in the osimertinib clinical trial program with no new safety signals.
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OA01 - Improving Outcomes in Locoregional NSCLC I (ID 892)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 107
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OA01.05 - Phase II Study of Neo-Adjuvant Chemo/Immunotherapy for Resectable Stages IIIA Non-Small Cell Lung Cancer- Nadim Study-SLCG (ID 12907)
11:15 - 11:25 | Presenting Author(s): Mariano Provencio
- Abstract
- Presentation
Background
The combination of chemotherapy and immunotherapy (CT-IO) has a high response rate and longer survival in unselected patients (pts) with metastatic non-small cell lung cancer (NSCLC). There are no data about this combination in the neoadjuvant setting.
a9ded1e5ce5d75814730bb4caaf49419 Method
A Phase II, single-arm, open-label multicenter study of local-advanced resectable stage IIIA N2-NSCLC adult patients with CT plus IO (nivolumab (NV)) followed by adjuvant treatment for 1 year. Neoadjuvant treatment: Three cycles of NV 360mg IV Q3W + paclitaxel 200mg/m2 + carboplatin AUC 6 IV Q3W. After completing neoadjuvant therapy, tumor assessment is performed in patients prior to surgery. Surgery is performed in the 3rd or 4th week after day 21 of the third cycle of neoadjuvant treatment. Adjuvant treatment: NV 240mg IV Q2W for 4 months and NV 480mg IV Q4W for 8 months (total one year) after surgical resection. The study aims to recruit 46 pts. The primary endpoint is Progression-Free Survival (PFS) at 24 months. Efficacy is explored using objective pathologic response criteria. We present preliminary data on patients that completed 3 cycles and underwent surgical resection.
4c3880bb027f159e801041b1021e88e8 Result
At the time of submission, 46 pts had been included and 20 underwent surgery. CT-IO was well-tolerated and surgery was not delayed in any patient. None of the pts was withdrawn from the study preoperatively due to progression or toxicity.
Twenty surgeries had been performed and all tumors were deemed resectable. The overall clinical response rate was 5% complete (CR) and 65% PR. The pathological response evaluated after surgery: 13 cases (65.0%) achieved CR (CPR) (95% CI 40.8-84.6%), and 3 (15.0%) had a major pathologic response (MPR), defined as <10% viable tumor cells in the resection specimen. Considering both CPR and MPR, the overall response rate was 80.0% (95% CI 56.3-94.3%) and 60% of complete responses were unsuspected
8eea62084ca7e541d918e823422bd82e Conclusion
This is the first multicentric study testing CT-IO in the neoadjuvant setting with promising antitumor activity in locally advanced, potentially resectable NSCLC yields an unprecedented complete pathologic response rate. The data will be updated at the time of the congress. EudraCT Number: 2016-003732-20
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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OA05 - Clinical Trials in IO (ID 899)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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OA05.06 - CheckMate 227: Patient-Reported Outcomes of First-Line Nivolumab + Ipilimumab in High Tumor Mutational Burden Advanced NSCLC (ID 13450)
14:25 - 14:35 | Author(s): Mariano Provencio
- Abstract
- Presentation
Background
The randomized, open-label, multipart phase 3 study CheckMate 227 (NCT02477826) demonstrated a significant progression-free survival benefit (co-primary endpoint) with first-line nivolumab+ipilimumab versus histology-based, platinum-doublet chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and high tumor mutational burden (TMB; ≥10 mutations/Mb). Patient-reported outcomes (PROs) for this population within CheckMate 227 are presented.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible chemotherapy-naïve patients had stage IV or recurrent NSCLC, ECOG performance status 0−1, and no known sensitizing EGFR/ALK alterations. PROs were assessed as an exploratory endpoint; this analysis included patients with high TMB randomized to nivolumab+ipilimumab or chemotherapy; specific outcomes included proportion of patients with disease-related symptom deterioration by 12 weeks and time to deterioration in symptoms (by Lung Cancer Symptom Scale [LCSS] Average Symptom Burden Index [ASBI]), and assessment of quality of life and overall health status (by EuroQoL-5 Dimension [EQ-5D] utility index [UI] and visual analog scale [VAS]). PROs were evaluated each cycle (Q2W, nivolumab+ipilimumab; Q3W, chemotherapy) for the first 6 months, every 6 weeks thereafter during treatment, and at follow-up visits 1/2. EQ-5D was also assessed during survival follow-up.
4c3880bb027f159e801041b1021e88e8 Result
PRO completion rates were ~90% at baseline and >80% for nearly all on-treatment assessments. Among patients with high TMB, fewer patients in the nivolumab+ipilimumab (n=139) versus chemotherapy (n=160) groups reported symptom deterioration by week 12, irrespective of whether they were still on therapy or had discontinued (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% CI: 2.4–22.5]). Time to first deterioration (TTD) using common assessment time points (on/off treatment) was delayed with nivolumab+ipilimumab versus chemotherapy for the LCSS ASBI (hazard ratio [HR]: 0.40; 95% CI: 0.26–0.63) and 3-Item Global Index (3-IGI; HR: 0.56; 95% CI: 0.38–0.82). The estimated benefit in TTD generally favored nivolumab+ipilimumab for individual symptoms in the ASBI and each item in the 3-IGI (HRs: 0.48–0.74), except for hemoptysis (HR: 1.20), which exhibited very low burden; an advantage for nivolumab+ipilimumab was also seen in the EQ-5D VAS (HR: 0.62; 95% CI: 0.42–0.92) and UI (HR: 0.50; 95% CI: 0.34–0.73). Mean changes from baseline with nivolumab+ipilimumab showed early and clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; for patients treated with chemotherapy, symptoms and quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following completion of chemotherapy (EQ-5D VAS).
8eea62084ca7e541d918e823422bd82e Conclusion
Nivolumab+ipilimumab demonstrated early and sustained improvements in health-related quality of life versus chemotherapy in patients with advanced NSCLC and high TMB.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-36 - Randomized Phase 2 Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer (ID 13960)
16:45 - 18:00 | Author(s): Mariano Provencio
- Abstract
Background
Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3), to block heregulin (HRG/NRG)-mediated ErbB3 signaling and induce receptor downregulation. This open-label, randomized Phase 1/2 study evaluated safety and efficacy of seribantumab in combination with erlotinib in advanced NSCLC. Here, we report the activity of seribantumab in combination with erlotinib, versus erlotinib alone, in patients with EGFR wild-type tumors and describe the potential predictive power of HRG.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with EGFR wild-type NSCLC were assigned randomly to receive seribantumab plus erlotinib or erlotinib alone. Patients underwent pre-treatment core needle biopsy, and archived tumor samples were collected to support pre-specified biomarker analyses.
4c3880bb027f159e801041b1021e88e8 Result
One hundred twenty-nine patients received seribantumab/erlotinib (n=85) or erlotinib alone (n=44). Median estimated PFS in the unselected ITT population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (HR=0.822; 95% CI, 0.37 to 1.828; P=0.63). In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the seribantumab/erlotinib combination (HR=0.35; 95% CI, 0.16 to 0.76; P=0.008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97 to 4.76; P = 0.059).
8eea62084ca7e541d918e823422bd82e Conclusion
The addition of seribantumab to erlotinib did not result in improved PFS in unselected patients. However, pre-defined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from seribantumab. An ongoing clinical trial is validating this finding in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216).
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P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.15-24 - Small Cell Lung Cancer: Clinical Characteristics and Survival of a Spanish Cohort of 221 Patients (ID 13200)
16:45 - 18:00 | Author(s): Mariano Provencio
- Abstract
Background
Lung cancer is the leading cause of death from cancer, of which 15% corresponds with small cell lung cancer (SCLC) subtype, directly related with tobacco. SCLC is the most aggressive subtype with an elevated percentage of metastatic patients at diagnosis and a poor prognosis.
a9ded1e5ce5d75814730bb4caaf49419 Method
A cohort of 221 patients diagnosed of SCLC were retrospectively analyzed in our center between 2008-2016.
Patient data was analyzed for baseline demographics and stage at diagnosis.
Progression free survival (PFS) and overall survival (OS) analysis were made comparing SCLC stage at diagnosis.
4c3880bb027f159e801041b1021e88e8 Result
The median age at diagnosis was 64 years and 74% were male, of whom 33% were older than 70 years. Only 0.5 % were never smokers and 16% had history of other malignancies, mostly related with tobacco. At diagnosis, 67% were metastatic and 88% symptomatic.
Complete baseline characteristics shown at Table 1.
PFS was 13.5 versus 6.83 months in located versus metastatic disease (p = 0.000) and median OS was 21.2 versus 8.5 months comparing located and metastatic stage (p = 0.000).
Kaplan-Meier curves shown at Image 1.
Table 1. Complete baseline characteristics. BASELINE CHARACTERISTICS ALL PATIENTS (n=221) SEX 164 (74%) male; 57 (26%) female AGE AT DIAGNOSIS 64 years (IQR 58-71); 65 years (IQR 59-73) male; 61 years (IQR 55-68) female. PATIENTS OLDER THAN 70 YEARS 72 (33%); 60 males and 12 females SMOKING HABIT Smoker --> 137 (61.9%)
Former smoker --> (> 365 days without smoking) à 81 (36.65%)
Never smoker --> 1 (0.45%)
Unknown --> 2 (0.9%)SMOKING PACK YEAR 58 pack/year; 60 pack/year male and 50 pack/year female AGE AT THE BEGINNING OF TOBACCO HABIT
16 years STAGE Stage I --> 10 (5%)
Stage II --> 8 (4%)
Stage III --> 53 (24%)
Stage IV --> 150 (67%)
ECOG 0-1--> 191 (86.4%)
2--> 23 (10.4%)
3--> 7 (3.2%)
CARDIOPULMONARY DISEASE COPD 23%
HBP 47%
DM 25%
DL 43%
Cardiopathy 19%HISTORY OF OTHER MALIGNANCIES 16%, most frequent: bladder cancer 7 (20.6%); head and neck cancer 6 (17.7%); lung cancer 4 (11.8%) FAMILIAR HISTORY OF LUNG CANCER 39% SYMPTOMS AT DIAGNOSIS Cough 42%; weight loss 30%; pain 28%; dyspnoea 27%; asthenia 21% TREATMENT 8.2% palliative treatment
91.8% active treatment (98.8% standard treatment with platinum-based chemotherapy and 1.2% clinical trial)PROGRESSION FREE SURVIVAL 13.5 (IQR 7.4-40.8) months in located and 6.8 (IQR 4.8-10.2) in metastatic disease compared with (p = 0.000)
OVERALL SURVIVAL 21.2 (IQR 10.8-39.6) months in located and 8.5 (IQR 3.9-15.5) in metastatic disease with (p = 0.000)
12 AND 24-MONTHS OVERALL SURVIVAL Located: 73% and 42% respectively
Metastatic: 33% and 15% respectively
8eea62084ca7e541d918e823422bd82e Conclusion
SCLC is mostly diagnosed at metastatic stage, but even in located disease prognosis is poor, so investigation is needed to improve PFS and OS.
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P2.03 - Biology (Not CME Accredited Session) (ID 952)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.03-15 - Integrin-Linked Kinase (ILK), Protein Tyrosine Phosphatase SHP2 and B lymphoma Mo-MLV Insertion Region 1 Homolog (Bmi-1) in EGFR-Mutant NSCLC (ID 12557)
16:45 - 18:00 | Author(s): Mariano Provencio
- Abstract
Background
The clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is jeopardized by the activation of multiple signaling pathways. ILK regulates the expression of Bmi-1, a well-known epithelial mesenchymal transition-inducing transcription factor. SHP2 function is required for MAPK pathway activation, and also plays a role in receptor tyrosine kinase signaling pathways.
a9ded1e5ce5d75814730bb4caaf49419 Method
Clinical data were assessed in accordance with the protocol approved by the institutional review board and de-identified for patient confidentiality. Pretreatment tumor specimens from advanced EGFR-mutant NSCLC patients (pts) were collected from eight sites in Spain, France, Italy and Colombia. mRNA gene expression analysis was performed by TaqMan (qRT-PCR). We examined the mRNA levels of ILK, SHP2 and Bmi-1.
4c3880bb027f159e801041b1021e88e8 Result
With a median follow-up of 26.7 months, median progression-free survival (PFS) was 9.3 (95% CI, 7.6-14.2) and 15.7 months (95%CI, 12.3-30.1) for pts with high and low ILK mRNA, respectively (P=0.0002), (HR for disease progression, 2.4; 95% CI, 1.3-4.5; P=0.002). Median PFS was 11.4 (95% CI, 8.2-14) and 24.1 months (95% CI, 8.2-30.9) for pts with high and low SHP2 mRNA, respectively (P=0.009), (HR, 2.4; 95% CI, 1.2-4.7; P=0.01). Median PFS was 8.2 (95% CI, 4.8-13.1) and 24.1 months (95% CI, 14.2-36.5) for pts with high and low SHP2 mRNA, respectively (P=0.001), (HR, 2.9; 95% CI, 1.4-5.9; P=0.002). Median overall survival (OS) was 17.9 (95% CI, 13.2-33) and 34.4 months (95% CI, 18.5-44.2) for pts with high and low ILK mRNA, respectively (P=0.200), (HR, 1.5; 95% CI, 0.79-3; P=0.200). Median OS was 18.5 (95% CI, 14-33) and 36.7 months (95% CI, 16.7-47.1) for pts with high and low SHP2 mRNA, respectively (P=0.018), (HR, 2.5; 95% CI, 1.1-5.8; P=0.020). Median OS was 17.6 (95% CI, 8.6-39.1) and 36.7 months (95% CI, 19.1-64.1) for pts with high and low Bmi-1 mRNA, respectively (P=0.004), (HR, 2.2; 95% CI, 1.0-5.1; P=0.040).
8eea62084ca7e541d918e823422bd82e Conclusion
The disturbance of RTKs, including ILK-SHP2-Bmi-1 axis, occurs frequently in EGFR mutant NSCLC patients, significantly limiting the PFS and OS. The levels of ILK, SHP2 and Bmi-1 could be predictive for upfront combinatory therapy of EGFR TKI plus a MAPK pathway inhibitor (SHP2 or MEK inhibitors).
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.15-25 - NIVEX TRIAL (GECP 1605): Nivolumab in the Real World: Spanish Expanded Access Program Experience in Pretreated Advanced NSCLC Patients (ID 13030)
16:45 - 18:00 | Author(s): Mariano Provencio
- Abstract
Background
Nivolumab is a standard treatment for pretreated patients with advanced non-small cell lung cancer (NSCLC). Real world data about toxicity and efficacy of nivolumab is needed.
a9ded1e5ce5d75814730bb4caaf49419 Method
We have analyzed patients from the Expanded Access Program in Spain that included patients with advanced pretreated NSCLC. We have retrospectively analyzed 665 patients that had received at least 1 dose of nivolumab 3mg/kg q2w from 01/2015 for squamous ﴾Sq﴿ and 06/2015 for non‐Sq NSCLC, to 11/2017.
4c3880bb027f159e801041b1021e88e8 Result
Median age was 61 (32-85) years, 73% were men, 85% had ECOG 0-1, 88% were current or former smokers and 15% presented brain metastases. 128 (19,2%) patients presented Sq NSCLC and 537 (80,8%) patients Non‐Sq NSCLC. 7% of patients presented EGFR mutation. PD-L1 was ≥ 1% in 32,9% of analyzed patients.
Best response was complete response 1,7%, partial response 22,4%, stable disease 24,1%, and progressive disease 37,1%, and was not assessed in 14,7% of patients. No differences in response rate were observed according to histology.
After a median follow‐up of 8,2 months, the median OS was 8,97 (95%CI 7,69-10,24) months, and the median PFS was 3,23 (95%CI 2,77-3,70) months. Estimated 1-year OS was 42,4% (95%CI 38,5-42,8%) and estimated 1-year PFS was 22,2% (95%CI 19,1-25,3%). No differences in OS or PFS according to histologies were observed.
296 (44,5%) patients presented toxicity related to Nivolumab, that was grade ≥3 in 69 (10,4%) patients. Grade ≥3 diarrhea was reported in 1,2% of patients and pneumonitis occurred in 1,2% of patients (1 patient presented a grade 5 pneumonitis). According to the presence of grade ≥3 toxicity, the median OS was 14,57 (CI95% 8,45-20,68) months for patients with grade ≥3 toxicity and 8,73 (CI95% 7,50-9,96) months for patients without grade ≥3 toxicity (p= 0,074).
Additional efficacy data including treatment lines, presence of immune-related adverse events, PS2, brain metastasis, response to first line, or post-nivolumab treatment will be presented.
8eea62084ca7e541d918e823422bd82e Conclusion
Efficacy and safety of nivolumab was in line with previously shown data. There was a trend to a better OS for those patients experiencing grade ≥3 toxicity.
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