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Joaquim Bosch-Barrera
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FP12 - Tumor Biology and Systems Biology - Basic and Translational Science (ID 188)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Tumor Biology and Systems Biology - Basic and Translational Science
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP12.01 - Circulating Tumor DNA to the Identification of EGFR Positive NSCLC Long-Term Survivors (ID 3013)
00:00 - 00:00 | Author(s): Joaquim Bosch-Barrera
- Abstract
Introduction
Survival data supports the use of first-line osimertinib as standard of care for EGFR positive non-small lung cancer (NSCLC). However, it remains unclear whether upfront osimertinib is superior to sequential first- or second-generation tyrosine kinase inhibitor (TKI) followed by osimertinib for all patients. The impossibility of predicting which patients are at high risk of progression constitutes a major limitation of the sequential TKI approach.
Methods
Seven hundred and forty-five plasma samples from 192 stage IV, EGFR positive NSCLC patients who were treated with first-line TKI were analysed by digital PCR.
Results
Patients with EGFR sensitizing mutations in plasma with mutant allele frequency (MAF) <7% before treatment initiation had median OS 37.9 months (25.3-NR), compared 17.5 (95%CI: 11.3-25.5) months for patients with MAF≥7% (adjusted HR=0.43; 95%CI: 0.25-0.76, respectively). OS was achieved with 53.1% of the patients treated with a 2nd line treatment other than osimertinib. In the multivariable analysis, undetectable levels of circulating tumour DNA (ctDNA) after 3 and 6 months of treatment were associated with improved PFS and OS (P<0.001 in all cases). Patients who became ctDNA negative after 3 or 6 months of treatment with MAF<7% at diagnosis had more than two-thirds lower risk of progression and death compare to the rest of patients (adjusted HR=0.28; 95%CI: 0.17-0.46 and HR=0.24; 95%CI: 0.12-0.48 for PFS and OS, respectively).
Conclusion
Pre-treatment ctDNA levels identify patients at low risk of progression and death who could benefit from sequential TKI treatment. Information regarding EGFR sensitizing mutation clearance could improve patient selection.
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MA01 - Novel Systemic Treatment in NSCLC (ID 102)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 11:45 - 12:45, Scientific Program Auditorium
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MA01.06 - Phase 2 of Pro-Autophagic Drug ABTL0812 in Combination With First-Line Paclitaxel and Carboplatin in IIIb/IV Squamous NSCLC (ID 2966)
11:45 - 12:45 | Presenting Author(s): Joaquim Bosch-Barrera
- Abstract
- Presentation
Introduction
ABTL0812 induces cytotoxic autophagy-mediated cancer cell death. It induces endoplasmic reticular (ER)-stress, and inhibits Akt/mTOR axis by upregulating TRIB3, an endogenous Akt inhibitor. Both actions, ER stress and blockade of Akt/mTOR, converge to induce a sustained and robust autophagy. Preclinical data in non-small cell lung carcinoma (NSCLC) indicated efficacy as a single agent and synergy with chemotherapy. A phase 1 of ABTL0812 in combination with paclitaxel and carboplatin (P/C) confirmed the safety of the triple combination
Methods
A single-arm phase 2 study was designed where ABTL0812 was administered 1300 mg TID orally with P/C 175 mg/m2/ AUC5 D1 every 3 weeks, for up to 8 cycles, followed by ABTL0812 as a maintenance until disease progression or unacceptable toxicity. The study enrolled patients with non-irradiable IIIb stage or stage IV squamous-NSCLC. Primary endpoint was overall response rate (ORR) by RECIST criteria v.1.1. Secondary endpoints were progression free survival (PFS), duration of response (DOR), safety and tolerability according to CTCAE v4.03 and pharmacokinetics (PK). Target modulation was assessed by two pharmacodynamic (PD) markers: TRIB3 and CHOP (an ER-stress biomarker) in blood.
Results
Thirty-seven patients were screened and 22 were evaluable. ORR was 54.5% (95% CI: 32.2-75.6%), median DOR was 4.9 months (95% CI: 1.4-14.5 months) and median PFS was 6.2 months (CI: 4.4-17.6 months). 91.4% of the pts had any type of adverse event (AE), and any type of related-AE appeared in 60% of the pts. Most frequent related hematological AE of the triple combinations were neutropenia (all grades 8.6%, grade≥3 8.6%), anemia (2.9%, 0%) and febrile neutropenia (2.9%, 2.9%). Most frequent related non-hematological AEs were asthenia (22.9%, 0%), diarrhea (22.9%, 0%), nausea (20.0%, 0%), dysgeusia (14.3%, 0%), and decreased appetite (11.4%, 0%). PK analysis at 4 weeks showed that Cmax is 6.4/5.1 mg/mL and t1/2 3.3/1.6 h for (-)/(+) ABTL0812 enantiomers. Increased TRIB3 and CHOP levels were observed up to 4 weeks after starting treatment.
Conclusion
The combination of ABTL0812+P/C compares favorably with historical controls. There is a trend to increased efficacy with no increased toxicity and an acceptable safety and tolerability profile. PK and PD profiles indicate sustained target modulation.
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MA08 - Advances in Biomarkers for Immune Checkpoint Blockade and Targeted Therapy in Non Small Cell Lung Carcinoma (ID 166)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/30/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA08.04 - LIPI and Outcomes of Durvalumab as Consolidation Therapy after ChRT in Patients with Locally-Advanced NSCLC (ID 1969)
16:45 - 17:45 | Author(s): Joaquim Bosch-Barrera
- Abstract
- Presentation
Introduction
The lung immune prognostic index (LIPI), which combines pretreatment derived neutrophils/[leukocytes minus neutrophils] ratio (dNLR) >3 and lactate dehydrogenase (LDH) > upper limit of normal (ULN), is associated with outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We aimed to assess whether pretreatment LIPI correlates with durvalumab efficacy after concurrent chemoradiotherapy in the locally advanced setting.
Methods
Multicenter retrospective study of locally advanced NSCLC patients treated with durvalumab consolidation in 21 European/US centers from 12/2015 to 5/2020. Clinical and biological data were collected before durvalumab treatment. PD-L1 expression by immunohistochemistry was also collected at diagnosis. LIPI was calculated according to previous reports and three groups were characterized: good (dNLR≤3+LDH≤ULN), intermediate (dNLR>3 or LDH>ULN) and poor (dNLR>3+LDH>ULN). The primary endpoint was progression-free survival (PFS). Response was assessed according to the clinical routine of each center.
Results
A total of 267 patients were enrolled. One hundred eighty-five (69%) patients were male, 252 (94%) smokers, with median age of 67 [range 59-73] and 223 (98%) with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1. 260/266 (98%) were stage III, of which 96 were IIIA, 127 stage IIIB and 37 stage IIIC. 163 (63%) had non-squamous histology and 12/131 (27%) harbored driver alterations: 5 EGFR, 4 BRAF, 3 MET, 2 ALK; missing in 136 cases. PD-L1 was ≥1% in 191/233 (82%) patients both from Europe and US, missing in 34 cases. LIPI was evaluable in 143 patients: 90 were considered good (63%), 50 intermediate (35%) and 3 (2%) as poor LIPI group. dNLR >3 was found in 47/218 (22%) and LDH > ULN in 23/143 (16%) cases. Radiotherapy was delivered concurrent in 219 (82%) of cases. No differences in clinical characteristics were found between 3 LIPI groups, including the response to previous chemoradiotherapy.
With a median follow-up of 13.4 months [95% confidence interval (CI), 12-15], the median PFS was 20 months [95% CI, 12.7-not reached (NR)]. Median PFS was 7.5 months [95% CI, 3.1-NR] for poor group vs. 10.7 months [95% CI, 5.1-NR] for intermediate group vs. 19.1 months [95% CI, 11.6-NR] for good LIPI group (P=0.020). Median overall survival (OS) was NR [95% CI 47-NR] in the entire cohort and therefore considered not mature. The first objective response rate under durvalumab was 44% (111/251), being 36% (18/50) for the intermediate-poor group and 38% (33/87) for the good group with no significant differences (P=0.099). No differences in PFS and OS between groups were found regarding PD-L1 status (P=0.5 and P=0.4, respectively).
Conclusion
Pretreatment LIPI is associated with clinical outcomes in locally advanced patients treated with durvalumab as consolidation after chemoradiotherapy. This cohort is still ongoing to confirm our preliminary findings in a larger cohort.
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P52 - Staging - Prognosis and Staging (ID 186)
- Event: WCLC 2020
- Type: Posters
- Track: Staging
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P52.10 - Profile of Comorbidities and Cancer History in Patients with mNSCLC in the Spanish Population (Thoracic Tumors Registry). (ID 3024)
00:00 - 00:00 | Author(s): Joaquim Bosch-Barrera
- Abstract
Introduction
Lung cancer is the most commonly diagnosed cancer worldwide and places a considerable burden on public health. The prognosis depends on the tumor stage and the clinical, histological and molecular characteristics. However, the comorbidities are also an important factor, not only in the diagnostic procedures but on the oncologic treatment strategies. The Thoracic Tumors Registry (RTT) of the Spanish Lung Cancer Group is a database that includes the data of patients with lung malignant neoplasms
Methods
The objective of this retrospective study is to describe the profile of comorbidities and cancer history in patients with NSCLC in the Spanish population.
Results
The total of patients included in the RTT is 12.897 (Aug 2016 - Jan 2020) and this report is based in the analysis of 5.049 of them. The median of age was 68,9-y (25-96). The most prevalent histology was the adenocarcinoma (72,2%) followed by the squamous cell carcinoma (SCC) (18,6%), others types include sarcomatoids, large cell, neuroendocrine and NOS carcinoma. Seventy-one percent of patients were male and 28,83% female and, according to the smoking habit, 42,42% were smoker, 41,06% former smoker and 15,56% never smoker. The asbestos exposure was informing in 108 cases (2,14%). A total of 4153 patients (82.25%) had comorbidities and these including: hypertension (50,13%), dyslipemia (34,36%), diabetes mellitus (22,9%), COPD (21,04%), heart disease (16,23%), depressive syndrome / anxiety (7,89%), vasculopathy (6,79%), obesity (4,94%), among others. 681 patients had a previous history of cancer (13,49%), the mains include the bladder and urinary tracts (14,39%), head and neck (10,43%), colorectal (10%), breast (8.08%), non-melanoma skin (6,31%), lung (2,5%), lymphoma (2,5%), among others.
Conclusion
Our study shows the real comorbidity profiles of patients with NSCLC in Spain. The cardiovascular and pulmonary diseases and the metabolic disorders are the most common pathologies in our patients. Theses comorbidities may have determined the selection of the treatment and influence the prognosis in lung cancer as well as and pose a major clinical challenge in the care of cancer patients.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.42 - OsimertinibTreatment in Non-Small Cell Lung Cancer (NSCLC) EGFR-T790M+. Activity in Patients with CNS Metastases. OSIREX (ID 1860)
00:00 - 00:00 | Author(s): Joaquim Bosch-Barrera
- Abstract
Introduction
Based on the lack of real-life results the Spanish Lung Cancer Group (SLCG) proposed to organize a retrospective study in which we can describe the experience in efficacy and safety of osimertinib in p with NSCLC EGFRm T790M and central nervous system CNS) metastases.
Methods
Observational, non-interventional, multicentre, one-arm, non comparative, retrospective study in T790M positive NSCLC p with advanced or metastatic disease. A total of 155 p were included. The observation period was from August 2016 to December 2018 in 30 Spanish hospitals. This corresponds to a total period of 29 months.
Results
155 p were included (108 women (69.7%), median age: 67 (37-88), 64% (99/155) were non-smokers and 99 % (154/155) had adenocarcinoma. Most p had received at least one prior treatment (97.4%, 151/155): 76.8% previous EGFR-TKIs, and 20.6% had received prior cytotoxic chemotherapy. At data cutoff, median duration of follow-up was 11.7 months (0.4-32).
A total of 155 p were evaluable for response analysis, 87(56%) as 1st and 2nd line therapy and 68 as ≥3rd line. 45 patients (30%) had CNS metastases at baseline. PFS was inferior en patients with CNS metastases than in those without (median, 7.2 months (95% CI, 3.9 to 10.6) vs 10.3 months (95% CI, 7.8 to 12.8) HR: 1.54 (95% CI, 1.03 to 2.32).
Conclusion
This retrospective study to assess the real-world clinical impact of osimertinib in p with advanced NSCLC and CNS metastases. Osimertinib had demonstrated greater penetration of blood brain barrier than gefitinib or erlotinib and these results could recommend us to use in first line.
