Virtual Library

Start Your Search

Gonzalo Recondo Jr.



Author of

  • +

    EP1.01 - Advanced NSCLC (ID 150)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
    • +

      EP1.01-76 - Oncomine Tumor Mutation Load Assay in NSCLC Patients from Argentina: Study Design and Feasibility (Now Available) (ID 2733)

      08:00 - 18:00  |  Presenting Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      High throughput next generation sequencing has improved the understanding of the genomic landscape of cancer. Somatic mutations throughout the exome derive in novel peptide sequences that can be recognized by the host immune system and drive immune responses in patients. The tumor mutational load (TML) is the number of somatic mutations per megabase of DNA and is an emerging biomarker to predict response to immune checkpoint inhibitors.

      Method

      The objective of this study was to evaluate the feasibility of assessing TML in tumors from patients with advanced NSCLC, treated with Nivolumab in second with Ion Torrent™ Oncomine™ TML Assay and compare it with TML from WES. The Oncomine TML is a targeted NGS assay that provides quantification of somatic mutations, from limited formalin-fixed, paraffin-embedded (FFPE) samples.

      Result

      DNA was purified with QIAamp DNA FFPE Tissue Kit (QIAGEN). We used a new Ion AmpliSeq targeted panel, derived from the Comprehensive Cancer Panel which covers approximately 1.7 Mb of genomic DNA and 409 genes, OTML in S5, Ion Proton (Life Technologies); and WES were performed in NovaSeq 6000 Sequencing System (Illumina). We included 40 patients with advanced NSCLC. 27 (68%) of patients had both, tumor and normal tissue to perform WES. FFPE samples were obtained from lungs (N=21), lymph nodes (N=11), pleura (N= 3), brain (N=1), skin (N= 1), bone marrow (N = 1), soft tissue (N=1). We used 20 ng of DNA to develop the manual library and templating. We covered a large genomic footprint to accurately measure somatic mutations, replacing the need for whole-exome sequencing (WES). Pipeline for analysis of the NGS output will be presented.

      Conclusion

      TML estimation with low DNA input requirements from FFPE samples is feasible. Up to 8 samples can be sequenced in a Ion 540™ Chip. Mutation load assessment can be done within 2–3 days. This assay was highly reproducible in FFPE samples. A detailed report provides normalized mutation count per MB as well as mutation signatures.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    EP1.04 - Immuno-oncology (ID 194)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
    • +

      EP1.04-41 - Efficacy of Immunotherapy in Elderly Patients with Non-Small Cell Lung Cancer: A Multicentric Experience from Argentina (ID 1900)

      08:00 - 18:00  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Immunotherapy (IO) has become a standard of care in NSCLC. Aging is associated with structural and functional changes in the immune system; hence, elderly patients could obtain less benefit from IO. Although randomized clinical trials showed benefit regardless of age, elderly are underrepresented, though its role in this population remains uncertain.

      Method

      We conducted a retrospective analysis of patients (pts) with NSCLC treated with IO at six centers between Nov 2013 and Feb 2019. We categorized patients in two groups (≥ 75 and < 75 years old) and evaluated overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Correlations were assessed using Fisher’s exact tests. Kaplan-Meier was used to estimate survival rates and compared using log-rank testing. Cox proportional hazard models were used to evaluate prognostic factors for PFS and OS.

      Result

      A total of 269 NSCLC pts treated with ICIs were included, 49 pts were ≥ 75 years old. Among them, 27 pts (55.1%) were male, 42 (85.7%) current or former smokers and 39 (79.5%) had PS 0-1; baseline brain metastases were present in 5 pts (10.2%). PDL-1 tumor proportion score (TPS) was ≥ 50% in 13/32 pts (41%), 31% received IO in first-line. There were no statistical significant differences in baseline characteristics between both groups. There was similar rate of G3-4 adverse events (18.4% vs. 17.7%, p=1.00) and treatment discontinuation (8.2% vs. 11% p=0.15, respectively) for ≥ 75 and < 75 years respectively. ORR was 18.4% (9/49) vs. 33.2% (73/220) p=0.06, DCR was 47% (23/49) vs. 65.9% (145/220) p=0.01, for ≥ 75 and < 75 years respectively. Median follow-up from IO was 15.9 months [95%CI 12.1 – 19.7]. Median PFS was 3.5 months [95%CI 2.4 – 4.6] vs. 9.8 months [95%CI 7.35 – 12.3] p<0.001 and median OS was 8.7 months [95%CI 5.4 – 12.0] vs. 18.8 months [95%CI 11.8 – 25.8] p=0.008, for ≥ 75 and < 75 years pts respectively. Histology (p=0.032), baseline corticoid treatment (p<0.001), first-line (p=0.004) and G3-4 toxicity (p=0.005) were significantly associated with OS in multivariate analysis.

      Conclusion

      In our cohort, immunotherapy demonstrated to be safe for elderly pts showing similar toxicity profile compared to their younger counterparts; however, elderly pts achieve less benefit than younger patients. Further assessment in larger cohorts is warranted, considering the high prevalence of lung cancer among this subset of patients.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    MA09 - EGFR & MET (ID 128)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • +

      MA09.11 - Mechanisms of Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14 Mutant Non-Small Cell Lung Cancer (Now Available) (ID 1421)

      15:15 - 16:45  |  Presenting Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Presentation
      • Slides

      Background

      Type I and II MET tyrosine kinase inhibitors (TKIs) are under development for patients with MET exon 14 mutant non-small cell lung cancer (NSCLC). Understanding the mechanisms driving resistance to MET TKIs is critical to design novel treatment strategies for this molecular subtype of NSCLC.

      Method

      Among patients with MET exon 14 mutant NSCLC treated with MET TKIs, pre- and post-TKI tumor tissue specimens and plasma samples were analyzed using next-generation sequencing (NGS) to explore genomic mechanisms of resistance upon disease progression.

      Result

      Between April 2014 to March 2019, 38 patients were treated with MET TKIs. Among these, paired samples from 15 individuals were evaluable for this study. Patients were treated with MET TKIs in the first-line (N=7; 46.7%), second-line (N=5; 33.3%), third-line (N=1; 6.7%) and fourth-line (N=2: 13.3%) setting. Eight patients were treated with one type I MET TKI and 7 patients received ≥2 MET TKIs. On target mechanisms of resistance were identified in 5 patients (33.3%), through secondary mutations in the MET tyrosine kinase domain (N=4) and MET amplification (N=1). Single MET kinase domain mutations D1228H/N were detected in 2 patients progressing on treatment with a type I MET TKI. In two cases, tumor tissue revealed only one resistance mutation (case #1 with Y1230H; case #2 with H1094Y), whereas paired plasma analysis demonstrated ≥3 resistance mutations in ctDNA (case #1 with G1163R, D1228N, Y1230H/S; case #2 with H1094Y, L1195F/V), reflecting the emergence of polyclonal on-target resistance. Off-target mechanisms of acquired resistance were identified in 7 patients treated with Type I MET TKI (46.7%) and involved amplification of EGFR (N=2), EGFR/HER2 (N=1), EGFR/HER3 (N=1), KRAS (N=1), EGFR/KRAS/BRAF (N=1), CCND1 (N=1). In 2 cases with bypass activation, sequential treatment with type II MET TKIs did not confer benefit. A concurrent NF1 mutation was present at baseline in a patient with primary resistance to MET TKI (6.7%). In 2 patients (13.3%), no genomic mechanisms of resistance were identified.

      Conclusion

      The landscape of resistance mechanisms to MET TKIs in NSCLC includes single and polyclonal secondary kinase domain mutations and bypass track activation by amplification of key oncogenes involving the ErbB/HER family of tyrosine kinase receptors and the MAPK signaling pathway. Given the complexity of resistance, therapeutic efforts to prevent acquired resistance in MET exon 14 mutant NSCLC should be developed.

      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    OA03 - Systemic Therapies for SCLC: Novel Targets and Patients' Selection (ID 121)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • +

      OA03.07 - Immune-Related Adverse Events and Clinical Outcome to Anti PD-1 Axis Inhibition in SCLC: A Multicenter Retrospective Analysis (Now Available) (ID 2880)

      13:30 - 15:00  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Presentation
      • Slides

      Background

      Immune-checkpoint inhibitors (ICIs) have shown promising activity in only a fraction of patients with small cell lung cancer (SCLC), and factors associated with clinical benefit are not well characterized. The development of immune-related adverse events (irAEs) may correlate with benefit from immune checkpoint inhibitors (ICIs) among patients with cancer. Whether an association exists between irAE development and improved clinical outcomes to ICIs in small cell lung cancer (SCLC) is unknown.

      Method

      We retrospectively analyzed data from five participating academic centers: the Dana-Farber Cancer Institute, East Carolina University, Columbia University, Beth Israel Deaconess Medical Center, and Johns Hopkins University. Patients with SCLC who received at least one dose of a programmed death (ligand) PD-(L)1 inhibitor alone or in combination with a cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitor were included in this study. To account for the time-dependent nature of irAE onset and clinical benefit from immunotherapy, we identified patients with early irAEs (defined as those occurring within 6 weeks of ICI treatment initiation) and performed a landmark analysis at this time point.

      Result

      Among 157 patients treated with ICIs, 65 (41.4%) experienced at least one irAE. Median time to the first irAE onset was 28 days (IQR:15-56). Baseline clinicopathologic characteristics were well balanced between patients who developed irAEs and those who did not. Median tumor mutational burden (TMB) was significantly higher among patients with irAEs compared to those without (14.4 vs 8.4 mutations/megabase [mut/Mb], P <0.01). Patients who developed at least one irAE had a significantly higher objective response rate (26.3% versus 3.3%, P <0.001), and significantly longer median progression-free survival (mPFS, 4.1 vs 1.3 months, HR: 0.30 [0.20-0.43, P <0.001]) and median overall survival (mOS, 14.1 vs 2.9 months, HR: 0.32 [0.21-0.48], P <0.001). The proportion of patients who were progression-free at 6, 9, and 12 weeks was significantly higher in patients who developed early irAEs compared to those who did not develop early irAEs (6 weeks: 89.5% vs 69.5%, P =0.01; 9 weeks: 71.1% vs 40%, P =0.001; 12 weeks: 65.8% vs. 31.6%, P <0.001). The median TMB was also significantly higher in patients who developed early irAEs (14.5 vs 8.7 mut/Mb, P <0.01).

      Conclusion

      Patients with SCLC treated with ICIs who developed early irAEs had a higher TMB and enhanced antitumor responses compared to those who did not develop irAEs. Whether a higher TMB is associated with the development of irAEs remains to be determined mechanistically.

      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 2
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.04-04 - DNA Damage Response Gene Alterations Are Associated with High Tumor Mutational Burden and Clinical Benefit from PD-1 Axis Inhibition in NSCLC (Now Available) (ID 2620)

      09:45 - 18:00  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      DNA damage response (DDR) gene alterations are associated with increased tumor infiltrating lymphocytes, higher genomic instability, and higher tumor mutational burden (TMB) in cancer. Whether DDR alterations are associated with benefit from immune-checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) is unknown.

      Method

      Clinicopathologic and genomic data were collected from patients (pts) with advanced NSCLC at the Dana-Farber Cancer Institute treated with PD-(L)1 inhibitors. Targeted next-generation sequencing (NGS) by OncoPanel was used to determine DDR gene mutation status and TMB. All loss-of-function alterations in DDR genes (including nonsense, frameshift, or splice site) were classified as pathogenic. Missense mutations were manually evaluated and classified as pathogenic if considered to be deleterious in the Catalogue of Somatic Mutations in Cancer (COSMIC) and ClinVar databases, as well as the PolyPhen-2 (Polymorphism Phenotyping v2) functional prediction tool.

      Result

      Of 223 pts with successful NGS who received ICIs, 116 (52.0%) were identified as having pathogenic DDR mutations (DDRpos) with alterations in the following genes: FANC genes (20%) ATM (13.9%), POL genes (11%), ERCC genes (8%), BRCA1/2 (8%), MLH1/MSH2/MSH6 (7%), CHEK1/2 (7%), RAD genes (6%), ATR (5%), BRIP1 (3%), XRCC genes (3%), BARD1 (2%), PMS (2%), NEIL (2%), BAP1 (1%), PALB2 (1%). DDRpos and DDR negative (DDRneg) groups were well balanced in terms of age, gender, histology, performance status (PS), smoking status, baseline presence of brain metastasis. The median TMB was significantly higher in the DDRpos group compared to the DDRneg group (12.9 vs 8.3 mutations/megabase [mut/Mb], P < 0.001), including among never smokers (11.0 vs 6.8 mut/Mb, P = 0.02). No difference in median PD-L1 expression was observed between groups (50% vs 50%, P = 0.52). Compared to DDRneg pts (N=107), DDRpos pts had a significantly higher objective response rate (30.4% vs 16.8%, P = 0.001), longer median progression-free survival (4.3 vs 2.3 months, HR: 0.64 [95%CI: 0.48-0.86], P = 0.003) and median overall survival (16.5 vs 11.2 months, HR: 0.62 [95%CI: 0.44-0.88], P = 0.008) with PD-(L)1 therapy. After adjusting for ECOG PS, smoking status, baseline brain metastasis, and line of therapy, DDRpos status was associated with significantly longer PFS (HR: 0.64 [0.48-0.86], P < 0.01) and OS (HR: 0.58 [95%CI: 0.41-0.83], P < 0.01) in multivariate analysis.

      Conclusion

      Pathogenic DDR alterations are frequent in NSCLC and are associated with higher TMB and improved clinical outcomes among NSCLC pts treated with PD-1 axis inhibition.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

    • +

      P1.04-82 - Toxicity as a Clinical Marker for Efficacy of Immunotherapy in NSCLC: A Multicentric Experience from Argentina (Now Available) (ID 1950)

      09:45 - 18:00  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Immunotherapy (IO) has become standard of care in NSCLC. Immune-related adverse events (irAEs) have shown to be associated with survival benefit in several tumor types in small reports. However, its predictive role as a clinical marker for efficacy to PD-1 inhibition in NSCLC remains uncertain.

      Method

      We conducted a retrospective analysis of patients (pts) with NSCLC treated with IO at six centers between Nov 2013 and Feb 2019. We categorized patients in two groups (irAEs and no-irAEs group) and evaluated overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). A 6-week cutoff was established to evaluate the impact of early vs. late onset of irAEs. Correlations were assessed using Fisher’s exact tests. Kaplan-Meier was used to estimate survival rates and compared using log-rank.

      Result

      A total of 269 NSCLC pts treated with ICIs were included, 48 pts (17.8%) developed Grade 3-4 irAEs. Among them, median age 66 years [range 47 - 86], 31 (65%) were male, 42 (87.5%) current or former smoker and 42 (87.5%) had PS 0-1, PDL-1 tumor proportion score (TPS) was ≥ 50% in 17/26 pts (65.4%), 5 pts (11%) received baseline corticoids; 15 pts (31%) were treated in first-line. No statistical significant differences in baseline characteristics were observed. Median follow-up from IO was 15.8 months [95%CI 12.1 – 19.7]. Median number of cycles to toxicity was 5 [range 1 – 60]. Most common grade 3-4 events were pneumonitis (n=12), adrenal insufficiency (n=7), thyroiditis (n=7), rash (n=6) and nephritis (n=6). There were 5 (10%) treatment-related deaths. Patients with irAEs had significantly higher ORR and DCR vs. no-irAEs: 48% (23/48) vs. 26.7% (59/221) p=0.005 and 83% (40/48) vs. 58% (128/221) p<0.001, respectively. Similarly, median PFS and OS were significantly prolonged in pts with irAEs vs. no-irAEs: 17.1 months [95%CI 8.1 – 25.9] vs. 6.6 months [95%CI 4.9 – 8.3] p=0.02 and 29.4 months [95%CI NR] vs. 12.9 months [95%CI 10.0 – 15.9] p=0.01, respectively. Early onset of irAEs (≤6 weeks) had significantly shorter PFS and OS vs. late onset (>6 weeks): 2.43 months [95%CI 0 - 9.02] vs 21.0 months [95%CI 14.57 - 27.44] p=0.006 and 3.94 months [95%CI NR] vs NR p=0.010, respectively.

      Conclusion

      In our cohort, we observed a correlation between irAEs and efficacy in NSCLC patients treated with IO. This potential predictive value needs to be validated in larger prospective cohorts to drive definitive conclusions.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.16-10 - Real-World Efficacy of First-Line Pembrolizumab in Patients with Advanced PD-L1 High Non-Small Cell Lung Cancer in Argentina (Now Available) (ID 1440)

      09:45 - 18:00  |  Presenting Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Pembrolizumab monotherapy is a standard first-line (1L) treatment regimen for patients (pts) with non-small cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) ≥ 50%. We aimed to study the clinical efficacy and toxicity of this approach in the real-world setting in Argentina.

      Method

      We conducted a retrospective, multicenter study. Patients with metastatic NSCLC and a PD-L1 TPS ≥ 50% treated in 1L with at least one dose of pembrolizumab monotherapy, from December 2016 to February 2019, were included. Data was collected from clinical records, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were estimated. Cox regression model was performed for uni- and multivariate analysis.

      Result

      A total of 53 pts were included. Median age (range) was 68 years (35-88), 33 (62.3%) were male, and 46 pts (86.7%) were smokers. Most tumors were lung adenocarcinoma (N=47, 88.7%), median (IQR) PD-L1 TPS was 79% (60-87.5) and 22 tumors (41.5%) had a TPS ≥ 75%. EGFR/ALK/ROS1 mutations/fusions were not detected. Brain (N=10; 18.9%), liver (N=5 (9.4%) and bone (N=15; 28.3%) metastasis were present at baseline. Performance status (PS) score was 0-1 in 46 pts (86.8%) and 7 pts (13.2%) had PS 2. Six pts received baseline corticosteroid treatment. The ORR with pembrolizumab was 41.5% (95% CI: 28.1-55.8), median PD-L1 TPS (mTPS) was significantly higher in responders (mTPS 74% vs 67%, P = 0.04). Grade ≥ 3 immune-related adverse events occurred in 7 pts (13.2%) and 10 (18.9%) required systemic therapy with steroids. With a median-follow up of 12.9 months (95% CI: 8.4-17.6), median PFS and median OS were not reached. The estimated percentage of patients alive and without progression at 6 and 12 months was 64.8% and 55.8%. The estimated percentage of patients alive at 6 and 12 months was 77.5% and 69.4%. Median PFS and OS for patients with PS 2 was 2.4 months (95% CI: 1.7-3.1) and 4.5 months (95% CI: 3.1-6.0), respectively. After adjusting for PS, a PDL1 TPS score ≥ 75% was independently associated with improved PFS in multivariate analysis [HR 0.28 (95% CI: 0.09-0.92); P = 0.03) but not with OS. PS score equal to 2 was independently associated with decreased OS [HR 4.52 (95% CI: 1.06-19.28); P = 0.04] in multivariate analysis.

      Conclusion

      Pembrolizumab monotherapy is tolerable and confers durable clinical benefit for patients with tumors expressing high levels of PD-L1 in the real world clinical setting. The optimal first-line immunotherapy approach for patients with PS 2 in this setting warrants further studies.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 3
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.04-32 - Comparison of Clinicopathological and Genomic Characteristics Between NSCLCs with a PD-L1 Tumor Proportion Score of ≥90% vs &lt;1% (Now Available) (ID 2618)

      10:15 - 18:15  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Determinants of PD-L1 expression in non-small cell lung cancer (NSCLC) are poorly defined. To identify characteristics associated with high vs. absent PD-L1 expression, we compared clinicopathologic and genomic features of NSCLCs at the two ends of PD-L1 expression spectrum: a PD-L1 tumor proportion score (TPS) of ≥90% or a PD-L1 TPS of <1%.

      Method

      We retrospectively collected clinicopathologic and genomic data (via targeted NGS) from consecutive NSCLC patients who had consented to an IRB-approved correlative research study and whose tumor PD-L1 TPS was either ≥90% or <1%. Single nucleotide variations, insertions/deletions, and copy number alterations were compared using Fisher’s exact test. Tumor mutational burden (TMB) was compared using Mann-Whitney test.

      Result

      421 NSCLCs with PD-L1 TPS ≥90% (N=133) or <1% (N=288) and successfully performed NGS were identified. There was no difference in age, sex, histology, or stage at diagnosis between the two groups. Patients with a PD-L1 TPS of ≥90% were more likely to be smokers (86.5% vs 76.4%; P=0.02) compared to patients with a PD-L1 TPS of <1%, and tumors in the PD-L1 TPS ≥90% group had higher TMB (10.89 vs 8.47 mutations/megabase; P=0.004) than those in the PD-L1 TPS <1% group. Tumors in the PD-L1 TPS ≥90% group were more likely to have KRAS (47.3% vs 31.3%; P=0.002), MET exon 14 (9.6% vs 2.1%; P=0.003), and TP53 mutations (71.0% vs 49.7%; P<0.001) than those in the PD-L1 TPS <1% group. Compared to the PD-L1 TPS ≥90% group, the PD-L1 TPS <1% group was more likely to have EGFR (23.6% vs 8.2%; P<0.001) and STK11 (23.4% vs 5.0%; P<0.001) mutations, as well as the absence of known oncogenic driver mutations (35.2% vs 24.8%; P=0.04). Chromosomal gain alterations (amplification or copy number gain) of the 9p24.1 locus, where the PD-L1, PD-L2, and JAK2 genes are located, were more common in the PD-L1 TPS ≥90% group than in the PD-L1 TPS <1% group (11.4% vs 2.8%, respectively; P<0.001). Chromosomal loss alterations (copy loss or deletion) of the 9p24.1 locus were more common in the PD-L1 TPS <1% than in the PD-L1 TPS ≥90% group (27.5% vs 3.8%, respectively; P<0.001). A repeated biopsy case showed acquired loss PD-L1 expression (PD-L1 TPS changed from 90% to 0%) with concomitant acquired loss of the 9p24.1 locus.

      Conclusion

      High PD-L1 expression in NSCLC is associated with tobacco use, high TMB, gain of the 9p24.1 locus and mutations in KRAS, MET exon 14, and TP53. PD-L1 negativity is associated with never smoking status, low TMB, loss of the 9p24.1 locus, mutations in EGFR and STK11, and the absence of oncogenic driver mutations.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

    • +

      P2.04-81 - Non-Small Cell Lung Cancer Treated with Immunotherapy: Multi-Institutional Experience from Argentina (Now Available) (ID 1893)

      10:15 - 18:15  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Immunotherapy (IO) has been established as the standard treatment for metastatic non-small cell lung cancer (NSCLC) patients improving survival. It has been approved both in first line and after platinum-treated patients. We aimed to study the efficacy and tolerability of anti PD-(L)1 inhibitors in pts with NSCLC in Argentina providing more evidence about efficacy and toxicity

      Method

      Metastatic NSCLC patients (pts) treated with immunotherapy in six hospitals between 11/2013 - 2/2019 were included. Data was collected retrospectively by the investigators. Progression-free survival (PFS) and overall survival (OS) were assessed. Cox-regression model was performed for uni- and multivariate analysis. All pts who received at least one dose of immunotherapy were evaluated for efficacy and toxicity.

      Result

      A total of 269 patients were included. Median age (range) was 66 ys (28-88), 164 (61%) were men, 226 (84%) were current/former smokers and 223 (82.9%) had performance status (PS) 0-1. The predominantly histology was non-squamous (N=239; 88.8%), 158 (58.7%) tumors were evaluable for PD-L1 expression and 9 (3.3%) had EGFR mutations. 86 (32%) pts received IO as first-line and 155(57.6%) as second-line therapy. Anti-PD1 antibodies were most commonly administered (83.3%). Baseline brain and liver metastases were present in 50 (18.6%) and 29 (10. 8%) pts, respectively. The overall response rate was 30.4% (76/256). The most common sites of progression were (N=261) bones 142 (54.4%), lung/lymph nodes 74 (28.4%) and brain 26 (10%), visceral 19 (7.3%). Grade ≥ 3 adverse events occurred in 48 pts (17.8%) and 28 (10.4%) pts discontinued treatment due to toxicity. With a median follow up of 15.88 months (95% CI 12.08-19.68), median PFS was 7.26 (95%CI 5.15-9.38) and OS was 15.18 (95%CI 9.47-20-90). In univariate analysis smoking status (p 0.049), PDL1 (p 0.002), PS (p 0.000), corticoid therapy at beginning of IO (p 0.001), grade≥3 toxicity (p 0.027), first line therapy (p=0.003) and driver mutation (p 0.028) were all associated with PFS. Age (p=0.030), PDL1% (p=0.007), corticoid therapy at beginning of IO (p<0.001), grade≥3 toxicity (p=0.012) and first line therapy (p=0.038) were all associated with OS. In multivariate analysis, PDL1 and PS were independently associated with both, PFS (p=0.011 and p=0.000, respectively) and OS (p=0.036 and p<0.001, respectively).

      Conclusion

      Treatment with anti PD-(L)1 inhibitors in the real-world is effective and tolerable, supporting the use of immunotherapy in pts with NSCLC. As previously reported, low PDL1 expression and poor PS confer worst clinical outcomes. Other factors such as age, line of treatment, corticoid use, toxicity and driver mutations may impact treatment response.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

    • +

      P2.04-82 - Discontinuation of Anti-PD-1/PD-L1 Antibody Therapy in the Absence of Disease Progression: Clinical Outcomes in Advanced NSCLC (Now Available) (ID 2024)

      10:15 - 18:15  |  Author(s): Gonzalo Recondo Jr.

      • Abstract
      • Slides

      Background

      Treatment with anti PD-1/PD-L1 immune checkpoint inhibitors (ICIs) prolongs survival in patients (pts) with advanced non-small cell lung cancer (NSCLC). Treatment discontinuation in the absence of disease progression rises concern on treatment efficacy in patients and providers. We aim to study the outcomes of patients with NSCLC who discontinued treatment with ICIs.

      Method

      Retrospective, multicenter descriptive study. Patients diagnosed with advanced NSCLC who discontinued therapy with pembrolizumab, nivolumab or atezolizumab in the absence of disease progression (PD) between 11/2013 - 2/2019 were included. All pts who received at least one dose of immunotherapy were evaluated for efficacy and toxicity.

      Result

      A total of 269 patients diagnosed with metastatic NSCLC and treated with anti-PD-1 or anti-PD-L1 antibodies were retrospectively studied. Median follow-up for the entire cohort was 15.8 months (95% CI: 12.08-19.68).

      Median age 66 ys (r 28-88), 61% men, 83,4% were former or current smokers. Non-squamous NSCLC was the most common histologic subtype (N=239; 89%).

      Performance status (PS) was 0-1 in 223 pts (83%), 86 pts (32%) received ICIs in first line, 154 pts (57.4%) in second line and 28 pts (10.6%) in third line or beyond. Pembrolizumab was the most common treatment for pts (N= 129; 48%), followed by nivolumab (N= 113; 42%) and atezolizumab (N=27; 10%).Within the entire cohort, 39 pts (14.5%) discontinued treatment with ICIs for reasons other than PD, 35 pts due to toxicity and 4 pts for other reasons. At the time of treatment discontinuation, 3 pts (7.7%) had achieved a complete response (CR), 10 (25.6%) a partial response (PR), 17 pts (43,5%) a stable disease and 9 (23%) had PD. Median duration of response after discontinuation of ICIs was 6 months (range 0.1-27).

      Of the CR + PR + SD subgroup at the time of analysis 76, 9% remain without PD.

      If we consider only patients who maintained at least 3 months’ therapeutic benefit when discontinuing treatment in the absence of PD, only 3 patients had PD (at 6, 7 and 17 months of discontinuation) and the median duration of response for this group was 8 months ( 3.74-27).

      Conclusion

      Patients who discontinue treatment with ICI in the absence of disease progression can achieve sustainable benefit. Further studies are needed to assess the safety and efficacy of reintroducing ICIs in the event of disease progression in this population.

      Only Active 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 or select "Add to Cart" and proceed to checkout.