Virtual Library
Start Your Search
Alessandra Curioni Fontecedro
Author of
-
+
MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
-
+
MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)
13:40 - 13:45 | Author(s): Alessandra Curioni Fontecedro
- Abstract
- Presentation
Background
Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.
4c3880bb027f159e801041b1021e88e8 Result
In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.
8eea62084ca7e541d918e823422bd82e Conclusion
Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.
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.
-
+
P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.01-79 - CheckMate 817: Safety of Flat-Dose Nivolumab Plus Weight-Based Ipilimumab for the First-line (1L) Treatment of Advanced NSCLC (ID 12004)
16:45 - 18:00 | Author(s): Alessandra Curioni Fontecedro
- Abstract
Background
CheckMate 227 demonstrated significant, clinically meaningful progression-free survival benefit with 1L nivolumab 3 mg/kg every 2 weeks (Q2W) plus low-dose ipilimumab 1 mg/kg Q6W vs chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and tumor mutational burden (TMB) ≥10 mutations/megabase. The dose and schedule for this combination regimen were optimized for 1L NSCLC in CheckMate 012 and further validated in CheckMate 568 and CheckMate 227. Flat dosing of nivolumab (240 mg Q2W) may simplify treatment while providing comparable exposure, and was recently approved for previously treated NSCLC. CheckMate 817 (NCT02869789) is a multi-cohort, open-label phase 3b/4 study evaluating the safety and efficacy of flat-dose nivolumab plus weight-based low-dose ipilimumab in recurrent/metastatic NSCLC. We report safety results from Cohort A, which evaluated this regimen in the 1L setting; updated results will be presented.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with ECOG PS ≤1 and previously untreated NSCLC were eligible, regardless of tumor programmed death ligand 1 (PD-L1) expression and TMB. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W were administered for 2 years or until disease progression/unacceptable toxicity. The primary endpoint was safety assessed by the incidence of grade ≥3 select treatment-related adverse events (TRAEs; defined as AEs of potential immunologic causes).
4c3880bb027f159e801041b1021e88e8 Result
Enrollment occurred between October 2016 and August 2017, with 391 patients initiating treatment at 68 academic and community-based centers in Europe and North America. Median age was 65 years and 27.9% of patients had squamous histology. PD-L1 expression was evaluable in 91% of patients; of these, 50% had ≥1% tumor PD-L1 expression. At database lock (March 1, 2018), minimum follow-up was 5.4 months and 34.5% of patients remained on treatment. The median (range) number of nivolumab and ipilimumab doses received were 9 (1–28) and 3 (1–10), respectively. Any grade and grade 3–4 TRAEs occurred in 74.4% and 27.6% of patients, respectively; 14.1% of patients discontinued treatment due to TRAEs. Rates of any grade select TRAEs by category ranged from 1.3% (renal) to 28.4% (skin). The most common grade 3–4 select TRAEs by category were hepatic (4.6%), pulmonary (3.1%), and gastrointestinal (3.1%). Two treatment-related deaths were reported; one due to Guillain-Barré syndrome and one due to rhabdomyolysis leading to heart failure.
8eea62084ca7e541d918e823422bd82e Conclusion
The safety profile of flat-dose nivolumab plus low-dose ipilimumab was consistent with previous reports of weight-based nivolumab plus low-dose ipilimumab optimized for NSCLC. Toxicities were manageable with no new safety signals identified.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.01-51 - Study of CD26/DPP4 Expression in a Large Series of Non-Small Cell Lung Cancer Patients (ID 13794)
16:45 - 18:00 | Author(s): Alessandra Curioni Fontecedro
- Abstract
Background
Lung cancer is a leading cause of cancer-related death worldwide and the prognosis remains poor CD26/dipeptidyl peptidase 4 (DPP4) is a transmembrane exopeptidase expressed on various hematopoietic but also somatic cells including malignancies of breast, colon, and mesothelioma. We previously found that the activity of CD26/DPP4 in human lung adenocarcinoma is four times higher than in normal lung tissue and the inhibition of CD26/DPP4 decreased the growth of lung tumors in experimental models. These data prompted us to analyze the expression of CD26/DPP4 in samples from lung cancer patients to unravel the role of CD26/DPP4 as a potential therapeutic target to reduce lung cancer burden.
a9ded1e5ce5d75814730bb4caaf49419 Method
To identify CD26/DPP4, we performed immunohistochemistry (IHC) on multi-organ tissue micro array (TMA) using four different antibodies. We finally selected the antibody produced by Cell Signaling Technology. For the analysis of CD26/DPP4 by IHC, TMAs constructed from the samples of non-small cell lung cancer patients were used. The cohort consisted of 1110 patients (Adenocarcinoma (AC): 567; Squamous carcinoma (SC): 443). Three pathologists independently scored the staining intensity from zero to three in a blinded manner. Lung AC cell lines from tissue (H2347, H522, A549, and Hop62) and pleural malignant effusion (H1437, H460, Mai9, and Gon8) were employed to assess the expression of CD26/DPP4. ELISA was used to quantify CD26/DPP4 from cell lines.
4c3880bb027f159e801041b1021e88e8 Result
Overall survival of the patients showed no difference between AC and SC groups. IHC scores revealed AC expressing significantly higher CD26/DPP4 levels vs. normal lung or SC (p=0.035, p<0.0001, respectively). In consistency with our previous findings, early stage cancer (IA) expresses significantly higher levels of CD26 than other stages IIB (p=0.0012), IIIA (p=0.0019), and IV (p=0.02) among AC samples. From our in vitro studies, we found that early stage derived cell line (H2347: stage I) expresses significantly more CD26/DPP4 compared to others (H522: stage II, A549 and HOP62 stage IV). In contrast, metastatic AC cell lines secrete significantly more CD26/DPP4 in culture medium compared to tissue derived cell lines, while the cellular level of CD26/DPP4 was higher in tissue derived cell lines.
8eea62084ca7e541d918e823422bd82e Conclusion
AC expresses significantly more CD26/DPP4 than SC. Furthermore, the expression of CD26/DPP4 was higher at early stages of AC compared to advanced stages. Human cell line data suggest that metastatic AC secretes CD26/DPP4 more actively than primary cancer. We therefore deem CD26/DPP4 to be a target for inhibition of human AC.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
-
+
P3.04-22 - Response of Brain Metastases in Patients with Non-Small Cell Lung Cancer Treated with Immunotherapy and Brain Directed Radiotherapy (ID 13407)
12:00 - 13:30 | Presenting Author(s): Alessandra Curioni Fontecedro
- Abstract
Background
The phase III trials of nivolumab, pembrolizumab or atezolizumab in comparison to standard chemotherapy for advanced non-small cell lung cancer (NSCLC) included a small number of patients with brain metastases. The aim of this study was to evaluate the radiological features of brain metastases after treatment with radiotherapy (RT) and immunotherapy (IT) in combination, as IT may synergize with RT.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed the clinical data and radiological findings from 27 patients with NSCLC receiving IT (nivolumab or pembrolizumab) and RT of brain metastases from June 2015 until August 2017 at the University Hospital of Zürich. Response to RT was assessed with magnetic resonance imaging in all patients and in case of non-unequivocal findings with 18F-Fluorethyltyrosin PET (FET-PET) in 6 patients.
4c3880bb027f159e801041b1021e88e8 Result
A total of 33 treatments with RT were applied (22 patients received one treatment, 4 patients 2, and 1 patient 3 treatments) of which 16 consisted of radiosurgery, 7 of hypofractionated stereotactic radiotherapy and 10 of whole brain radiotherapy. 23(85.2%) patients received nivolumab and 4 (11.1%) pembrolizumab. RT was performed in 36% of the cases (12 out of 33) during IT, in 61% (20 out of 33) before, and 3% (1 out of 33) after IT. In cases where RT was performed before, the median time to IT was 6.5 months. 22 (81.5%) patients had an adenocarcinoma and 5(18.5%) sqamous cell histology. Response of brain metastases was assessed after completion of treatment: in 6 out of 33 treatments (18.2%) a complete response was achieved, in 14 (42.4%) a partial response, in 2(6.1%) a mixed response, in 2 patients (6.1%) a progression of disease and in 4 (12.1%) a pseudoprogression was observed. FET-PET was performed when pseudoprogression was suspected (6 patients) and perfusion curves helped differentiating between pseudoprogression (4 out of 6 patients) and true progression (2 out of 6 patients). Median overall survival was 17.8 months (95%CI: 2.9-32.6).
8eea62084ca7e541d918e823422bd82e Conclusion
Peudoprogression of brain metastases, defined as initial enlargement of tumor lesions and then decrease in size, should be considered in patients treated with immunotherapy and radiotherapy of brain metastases from NSCLC. Dynamic FET-PET patterns may help differentiating pseudoprogression and true progression. In cases of pseudoprogression, immunotherapy can be safely continued without additional interventions on brain metastases.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
PC01 - Controversies in Mesothelioma (ID 840)
- Event: WCLC 2018
- Type: Pro-Con Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 205 AC
-
+
PC01.01 - PRO Intrapleural Chemotherapy Is It the Future? (ID 11598)
10:30 - 10:45 | Presenting Author(s): Alessandra Curioni Fontecedro
- Abstract
- Presentation
Abstract not provided
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.
