Virtual Library
Start Your Search
P. Garrido
Author of
-
+
MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
-
+
MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (ID 4712)
15:32 - 15:38 | Author(s): P. Garrido
- Abstract
- Presentation
Background:
Trials of anti-EGFR necitumumab and anti-PD1 pembrolizumab demonstrate the anti-tumor activity of each agent in NSCLC.
Methods:
Single-arm, multicenter Phase 1b study to investigate effectiveness and safety of necitumumab combined with pembrolizumab in patients with Stage IV NSCLC (NCT02451930). In Part A, escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W. In the absence of dose limiting toxicity, Part B (expansion cohort) was planned with necitumumab 800 mg in 27 squamous and 27 nonsquamous NSCLC patients. Major eligibility criteria included: progression after ≥1 platinum-based chemotherapy, and ECOG PS 0-1. Study objectives were to evaluate tolerability and ORR by RECIST 1.1. PD-L1 status was centrally assessed using PD-L1 IHC 22C3 pharmDx assay (considered negative, weak positive, strong positive if <1%, 1-49%, ≥50% of tumor cells were stained, respectively).
Results:
The interim analysis population includes 34 nonsquamous patients (median age 61 years, 68% men, 21% never smokers, PD-L1 status: negative, 50% [17/34]; positive weak/strong, 15% [5/34]/15% [5/34]; unknown 21% [7/34[BJ1] ]). Median follow-up was 6.0 months. Ten patients (29.4%) had PR (confirmed and unconfirmed) (PRs by PD-L1 status: negative, 18% [3/17]; positive weak/strong, 60% [3/5]/40% [2/5]; unknown status, 2 patients). DCR was 67.6%. PFS rate at 6 months was 55.1% (95% CI, 36.2-70.6); median PFS was 6.9 months (95% CI, 2.7-NR). Most common Grade ≥3 AEs were skin rash (9%), hypomagnesemia (9%), VTE (9%) and increased lipase (9%); 1 patient died due to an AE (respiratory tract infection). Five patients (14.7%) discontinued therapy because of an AE. Figure 1
Conclusion:
Safety profile corresponds to individual profiles for both drugs, with no additive toxicities. These preliminary data suggest activity of this combination in a pretreated nonsquamous NSCLC population, irrespective of PD-L1 status.
Only 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.
-
+
P1.01 - Poster Session with Presenters Present (ID 453)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P1.01-004 - Is There Any Role of Residential Radon in Non Small Cell Lung Cancer (NSCLC) Patients Harboring Molecular Alterations? (ID 4770)
14:30 - 14:30 | Author(s): P. Garrido
- Abstract
Background:
Radon gas is the first cause of lung cancer in non-smoking population. The World Health Organization (WHO) recommends radon concentration lower than 100 Bq/m3. In recent years, most of the advances in personalized therapy in NSCLC patients also occurred in non-smokers. Furthermore, limited information is available about the clinical and pathological characteristics in patients exposed to radon gas. We hypothesized that residential radon could be associated to some specific pathological and molecular alterations in NSCLC patients.
Methods:
Prospective study of a cohort of NSCLC patients harbouring molecular alterations (EGFR, BRAF mutations (m), ALK and ROS1 rearrangements (r)) in our centre, between September 2014 and October 2015. A radon detector alpha-track was given to each patient to measure residential radon concentration for 3 months; it was analysed using optical microscopy. We collected demographic information, smoking history, environmental exposure and clinical characteristics. The pathologic characteristics were prospectively revised by a lung cancer pathologist, including histology pattern, grade and inflammatory infiltrate. EGFR and BRAF mutation (m) were analyzed using quantitative real-time polymerase chain reaction (PCR) and ALK and ROS1 rearrangement by fluorescence in situ hybridization (FISH). Data was analyzed using IBM SPSS v.20.
Results:
60 detectors were delivered (10% missing), 48 patients were evaluated (89.6% living in Madrid). Median age 66.5 (29- 82); 33 (68.8%) females; 33 non-smokers (31.3% passive smokers and 35.4% childhood exposure) and 3 (6.3%) light smokers. 100% adenocarcinoma (35.4% mixte, 18.8% acinar, 10.4% solid, 8.3% papillary, 8.3% micropapilllary, 8.4% others and 10.4% unknown); EGFRm 36 patients, ALKr 10 patients and BRAFm 2 patients. Home characteristics measured: 79.2% flat (89.1% measurement at bedroom); building material: 89.6% bricks. Median length of stay was 28 years (2-55). Median height of house 2 floors (0-15). Median of radon concentration: 104 Bq/m3 (42- 915); 60.42% over WHO recommendation. By molecular alteration: EGFRm median 96 Bq/m3 (42-915), ALKr median 116 (64-852) and BRAFm median 125 (125). A significant association was observed between non-EGFR mutation and concentration over the WHO recommendation (p=0.044). In univariant analysis, radon concentration was associated with non-mucinous histology and low tumoral grade (p=0.033 and p=0.023, respectively).
Conclusion:
Our final results have shown no consistent association between residential radon and molecular alterations in NSCLC patients, but a trend has been suggested in ALKr and BRAFm. Large multicenter studies are needed to confirm this hypothesis.
-
+
P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02c-075 - Could Blood Levels of Lymphocytes and Eosinophils Help Us to Identify the Efficacy or Toxicity of Immunotherapy? (ID 5960)
14:30 - 14:30 | Author(s): P. Garrido
- Abstract
Background:
Immune checkpoint blockade have demonstrated durable responses and improvement in overall survival (OS) in approximately 20% of unselected patients with advanced non-small cell lung cancer (NSCLC). To develop reliable, validated biomarkers to identify those subgroups of patients most likely to benefit remains a challenge.
Methods:
We retrospectively analyzed pretreated advanced NSCLC patients (p) receiving anti-PD1 or anti-PDL-1 inhibitors at our institution. The immune-related response Criteria (IRC) was used for response evaluation. Basal and at 6 weeks lymphocytes and eosinophils counts were correlated with efficacy and toxicity.
Results:
44 p were treated between April 2014 and December 2015. We realized evaluation of response in 40 p. 13 p received Atezolizumab, 23 p Nivolumab and 4 p Pembrolizumab. Patients characteristics: 68% males, median age 63 years, 62 % non-squamous histology, 3 % never-smoker, PS 0/1/2 in 43/50/7%. The molecular status assessed in 32 p (KAS mutation 10p). Immunotherapy was the second-line treatment in 26p with a median number of doses received of 5 (range 2-27). Median OS was 12 months (95%CI 3–21) and median PFS was 4 months (95%CI 0.7–7) from the start of checkpoints inhibitors. Overall survival rate at 12 months was 40%. Immune-related adverse events were observed in 15p (37.5%), including 7 grade 3–4 events (17.5%). No drug-related death occurred. We found that there was a significant association between the risk of toxicity and the increased number of eosinophils between the first reassessment and the baseline measurement OR 6, p 0.014. At the time of the first reevaluation, 28p had progression disease (PD), 6 partial response (PR) and 6 stable disease(SD). In 22/28p with progression at first evaluation, CT was realized ≥4 weeks. Pseudoprogression was confirmed in 6/22p (21%). No differences were found in response by gender, ECOG, histology, KRAS status, smoking status, antiPD-1 vs antiPD-L1, or drug used. 15/18p with clinical benefit (PR+SD+pseudoprogression) had basal level of eosinophils ≥100 mm3, (p 0.003 OR 0.114) whilst correlation between response and basal lymphocytes was not statistically significant (p 0.35 OR 0.58). One of 18p with clinical benefit had levels of lymphocytes at the first evaluation <1000 mm3 versus 10/22p with PD(p 0.013, HR 0.13) whilst levels of eosinophils ≥100 mm3 at the first evaluation was not statistically significant (p 0.052 HR 0.26).
Conclusion:
Our very preliminary results suggest that lymphocytes and eosinophils could help us to characterize activity and toxicity of immunotherapy treatments. Further studies are guaranteed.
-
+
P3.02c-102 - Safety and Tolerability of Abemaciclib Combined with LY3023414 or with Pembrolizumab in Patients with Stage IV NSCLC (ID 4625)
14:30 - 14:30 | Author(s): P. Garrido
- Abstract
Background:
Currently, treatment options are limited for patients with advanced and/or metastatic NSCLC particularly after initial treatment. In a prior phase 1 study, abemaciclib, a CDK4 & 6 inhibitor, demonstrated single-agent anti-tumor activity when dosed orally on a continuous schedule, with an acceptable safety profile in patients with previously treated metastatic NSCLC (NCT01394016). PI3kinase is an escape pathway after CDK inhibition in tumor models and aberrant immunity is a hallmark of cancer, providing the rationales to combine abemaciclib with PI3K and with checkpoint inhibitors. An ongoing Phase 1b multicenter, open-label, 3+3 dose-escalation trial with an expansion phase is investigating abemaciclib in combination with multiple single-agent options in metastatic NSCLC (NCT02079636). Here we report preliminary results for two arms of the study.
Methods:
In Part D, abemaciclib was administered orally on a continuous schedule every 12 hours (q12h) in combination with the PI3K/mTOR inhibitor, LY3023414, at 100, 150, or 200 mg q12h. In Part E, abemaciclib was administered in combination with the anti-PD-1 antibody, pembrolizumab (200 mg I.V. infusion q3 weeks). Patients with late stage NSCLC and 1-3 prior therapies without central nervous system metastasis were treated until disease progression or other discontinuation criteria were met. Primary endpoints for each cohort included safety/tolerability and identification of the recommended phase 2 dose. Safety assessments followed the Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0). Parts D and E began enrolling patients on April 13, 2015 and April 29, 2016, respectively.
Results:
As of August 24, 2016, Parts D and E escalation included, respectively, 22 [male (64%)/Caucasian (77%)/stage IV (91%)/adenocarcinoma (91%)] and 6 patients [male (33%)/Caucasian (100%)/stage IV (67%)/adenocarcinoma (100%)]. ECOG PS was ≤1 in both cohorts. In Part D, 1 patient on dose level-2 (DL-2) experienced a dose limiting toxicity (DLT) (G4 thrombocytopenia). Evaluation of additional dose levels is ongoing. Seventeen patients (77%) experienced ≥1 treatment-related emergent adverse event (TRAE). Common TRAEs were nausea (50%), diarrhea (50%), vomiting (36%), fatigue (32%), and decreased appetite (27%). In Part E, no DLTs or deaths occurred in the two dosing cohorts evaluated. Four patients (67%) experienced ≥1 TRAE with 75% G1/2. Common TRAEs included fatigue (50%), diarrhea and proteinuria, (33%, each).
Conclusion:
The majority of previously treated advanced/metastatic NSCLC patients administered abemaciclib with LY3023414 or with pembrolizumab had manageable and tolerable adverse events, similar to those of the single agents.
