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  • 1
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    Prognostic and predictive implications of plasma ctDNA in guiding first-line targeted therapy for metastatic HER2 -mutant non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9052-9052
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9052-9052
    Abstract: 9052 Background: Trastuzumab deruxtecan (T-DXd) is the first HER2-targeted drug approved for NSCLC with human epidermal growth factor receptor 2 ( HER2, ERBB2) mutation in the second or later line settings. However, the optimal first-line treatment for these patients remains unclear. Access to rapid tissue sequencing is not always available, thus presenting challenges to first-line drug development. Circulating tumor DNA (ctDNA) analysis has the potential to overcome these obstacles to guide optimal first-line targeted therapy for patients with HER2-mutant NSCLC. Methods: We retrospectively analyzed patients with metastatic HER2-mutant NSCLC who underwent prospective clinical ctDNA sequencing at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to September 2022. HER2 mutations were identified by next-generation sequencing through MSK-IMPACT, MSK-ACCESS or Resolution ctDx Lung. Results: We identified 64 patients with metastatic HER2-mutant NSCLC who had received at least one line of systematic therapy. The median age was 63 years (range: 23–90), and there were more women (n = 38, 60%), and never-smokers (n = 38, 60%). The activating HER2 mutations included exon 20 insertions (73%), exon 8 (11%), 19 (11%), and 20 SNVs (5%). Plasma ctDNA was tested before initial therapy in 40 patients with a median overall survival (OS) of 28 months (95% CI 21-34), in whom 31 patients (78%) had at least one detectable ctDNA alteration by MSK-ACCESS and ctDx Lung. 55% (17/31) received chemoimmunotherapy with pembrolizumab as the first-line treatment. The median time to treatment discontinuation (TTD) was 6 months (95%CI 5.5-6.9). Additionally, 19% of patients (6/31) received a HER2-targeted antibody-drug conjugates (ADC) as first-line treatment with a median TTD of 6 months (95% CI 2-10), including 5 with T-DM1 and one who received first-line T-DXd treatment with a TTD of 9 months. Patients with baseline ctDNA alterations had significantly shorter OS (hazard ratio (HR), 5.25; 95% CI, 1–24; p = 0.019). Conclusions: Baseline plasma ctDNA has the potential to guide first-line targeted therapy for patients with HER2-mutant NSCLC. As an independent negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies to avoid underestimating the effects of therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9052
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Molecular correlates of PD-L1 expression in patients with non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 9018-9018
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9018-9018
    Abstract: 9018 Background: PD-L1 expression is the only FDA-approved predictive biomarker for patients with NSCLC treated with immune checkpoint inhibitors. The impact of tumor molecular profiling on tumor PD-L1 expression is not known. We hypothesized that somatic mutations and copy number alterations may be associated with distinct patterns of PD-L1 expression in patients with NSCLC. Methods: We examined patients with NSCLC in whom PD-L1 testing and targeted next-generation sequencing (MSK-IMPACT) were performed on the same tissue sample. PD-L1 expression was determined by IHC using the E1L3N antibody clone and categorized as PD-L1 high (≥ 50%), intermediate (1-49%), or negative ( 〈 1%) expression. The association of PD-L1 with individual genes, pathways, tumor mutation burden, whole genome duplication (WGD), and aneuploidy (fraction of genome altered (FGA)) were evaluated. P-values 〈 0.05 and q-values 〈 0.15 were considered significant for individual genes. Results: 1023 patients with NSCLC had PD-L1 testing and MSK-IMPACT performed on the same tissue sample, 18% (n = 180) had high, 21% (n = 218) had intermediate, and 61% (n = 625) had negative PD-L1 expression. High PD-L1 expression was significantly enriched in metastatic vs primary lesions (p 〈 0.001). There was a minor correlation between PD-L1 and TMB (spearman rho = 0.195) and PD-L1 and FGA (spearman rho = 0.11). Similar rates of WGD were found among patients with high, intermediate, and negative PD-L1 expression (p = 0.38). Mutations in KRAS and TERT were significantly enriched in PD-L1 high compared to other groups (p = 0.001, q = 0.14; p 〈 0.001, q = 0.003). By contrast, mutations in EGFR and STK11 were associated with PD-L1 negativity (p 〈 0.001, q = 0.001; p = 0.001, q = 0.14). Pathway analysis showed DNA repair (p 〈 0.001), TP53 (p 〈 0.001), and SWI/SNF (p = 0.04) pathways significantly associated with PD-L1 high compared to PD-L1 negative expression. Conclusions: The genetic features of NSCLC are associated with distinct patterns of PD-L1 expression. This data may provide insight to how the molecular phenotype can interact with the immunologic phenotype of tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.9018
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
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    Efficacy of platinum-pemetrexed combination chemotherapy in ALK + non-small cell lung cancer refractory to second-generation ALK TKIs.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 9067-9067
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9067-9067
    Abstract: 9067 Background: Second-generation (gen) ALK tyrosine kinase inhibitors (TKIs) are standard first- and second-line therapies in patients (pts) with advanced ALK+ non-small cell lung cancer (NSCLC). After progression on second-gen TKI(s), standard options include platinum (PT)-based chemotherapy (chemo) or the third-gen ALK TKI lorlatinib. The efficacy of PT-based chemo is established in treatment-naive pts but is undefined in pts who have failed prior ALK TKIs. Here we evaluate the efficacy of PT/pemetrexed (pem)-based chemo in pts with ALK+ NSCLC refractory to second-gen TKIs. Methods: A retrospective study was performed at three institutions. Pts were eligible if they had advanced ALK+ NSCLC refractory to ≥1 second-gen TKI, and received PT-pem-based chemo. Medical records and imaging were reviewed to determine outcomes. Results: Among 55 eligible pts, chemo regimens included: PT/pem (31/55, 56%), PT/pem/bevacizumab (bev) (6/55, 11%), PT/pem/PD-1 inhibitor (3/55, 5%), PT/pem with ALK TKI (8/55, 15%), PT/pem/bev with TKI (6/55, 11%), and PT/pem/PD-1 inhibitor with TKI (1/55, 2%). Pts had received one (6/55, 11%), two (38/55, 69%), or more (11/55, 20%) prior TKIs. Six pts (11%) previously received adjuvant or neoadjuvant chemo. Radiographic data for response evaluation was available for 39 pts. Among 36 pts with measurable baseline disease, confirmed ORR was 31% (11/36; 95% CI, 16-48%); 13 (36%) had stable disease. The median duration of response was 5.4 months (95% CI, 1.5-7.1 months). The median progression-free survival (PFS) for the entire cohort was 4.0 months (95% CI, 2.8-4.6 months). Chemo (PT/pem +/- bev or PD-1 inhibitor) plus ALK TKI (n = 15) was associated with a significant increase in PFS compared to chemo without TKI (n = 40) (median PFS 6.8 vs 3.2 months; HR 0.306; p = 0.002). Similarly, PT/pem plus ALK TKI (n = 8) was associated with increased PFS compared to PT/pem without TKI (n = 31) (median PFS 6.8 vs 2.9 months; HR 0.358; p = 0.036). Conclusions: The efficacy of PT-pem-based chemo is limited after failure of second-gen ALK TKIs but may be higher in pts who receive chemo plus ALK TKI, suggesting a potential role for ongoing ALK inhibition. The modest benefit of PT-pem-based chemo highlights the need for other therapeutic strategies for pts refractory to second-gen TKIs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.9067
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
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    YES1 amplification as a primary driver of lung tumorigenesis and YES1/YAP1 amplifications as mediators of acquired resistance (AR) to ALK and EGFR tyrosine kinase inhibitors (TKIs).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21591-e21591
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21591-e21591
    Abstract: e21591 Background: Our previous work identified YES1 amplification as a mechanism of AR to EGFR TKIs. The current study investigates the potential role of YES1 amplification as a primary driver of tumorigenesis and of YES1/YAP1 amplifications as mediators of AR to ALK and EGFR TKIs. Methods: Models of ectopic expression were established and characterized for YES1 and YAP1 in human bronchial epithelial cells (HBECs) and ALK fusion-positive ( ALK+) and EGFR-mutant ( EGFRm) lung adenocarcinoma (LUAD) cell lines. MSK-IMPACT data for all LUAD cases and for ALK and EGFR TKI AR cases were surveyed for YES1 and YAP1 amplification. Results: YES1 was found to be amplified in 0.5% of all LUAD cases currently in the MSK-IMPACT database. To demonstrate its potential as a primary driver of tumorigenesis, YES1 was inducibly expressed in HBECs and shown to promote EGF-independent growth, focus formation, and increases in proliferation rate and sensitivity to Src family kinase (SFK) TKIs. Consistent with these findings, a partial response by RECIST criteria to third-line dasatinib was observed for a patient with stage IV LUAD in which MSK-IMPACT detected YES1 amplification and no established primary driver alteration. In models of AR, overexpression of either YES1 or YAP1 in multiple ALK+ and EGFRm cell lines conferred resistance to ALK and EGFR TKIs. Sensitivity to ALK or EGFR TKIs was partially recovered in YES1-overexpressing cells lines by siRNA-mediated gene knockdown of YAP1, and was restored in YAP1-overexpressing cells lines by knockdown of YES1 or mutation of the YES1-phosphorylation site on YAP1. ALK + or EGFR m cells overexpressing either YES1 or YAP1 were sensitive to dual inhibition of the primary driver and SFKs with single-agent repotrectinib or dasatinib, respectively. In contrast, treatment of YAP1-overexpressing ALK+ H3122 cells with alectinib induced changes in morphology and gene expression consistent with epithelial-to-mesenchymal transition (EMT) and rendered the cells insensitive to repotrectinib. Similar resistance to dual inhibition was seen in other YAP1-overexpressing cell lines after treatment with only ALK or EGFR blockade. To date, one LUAD case each of EGFR and ALK TKI AR has been found through MSK-IMPACT™ to be associated with YAP1 amplification. Conclusions: SFK inhibition can potentially be exploited to therapeutically target YES1 amplification as a primary driver in tumorigenesis and YES1/YAP1 amplifications as mediators of AR to ALK and EGFR TKIs.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21591
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 5
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    Master protocol to assess safety and recommended phase 2 dose of next generation NY-ESO-1–specific TCR T-cells in HLA-A*02 patients with synovial sarcoma or non-small cell lung cancer (Substudies 1 and 2).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS2661-TPS2661
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS2661-TPS2661
    Abstract: TPS2661 Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy using a genetically modified T-cell receptor (TCR) to improve recognition of cancer cells expressing NY-ESO-1/LAGE-1a. Next generation NY-ESO-1 TCR T-cell therapies, such as GSK3901961 and GSK3845097, integrate added genetic modifications to enhance anticancer activity. GSK3901961 co-expresses the CD8α chain to stabilize TCR-human leukocyte A (HLA) class I interactions on CD4+ T cells, improving T-cell persistence and helper functions such as Type 1 T-helper antitumor responses. GSK3845097 co-expresses a dominant negative transforming growth factor-β (TGF-β) type II receptor to reduce TGF-β pathway activation and maintain T-cell proliferation, cytokine production, and cytotoxicity in the tumor microenvironment. A first-time-in-human master protocol (NCT04526509) will evaluate safety, tolerability, and recommended phase 2 dose (RP2D) of these and possible subsequent therapies. Substudy 1 will assess GSK3901961 in patients (pts) with advanced non-small cell lung cancer (NSCLC) or synovial sarcoma (SS). Substudy 2 will assess GSK3845097 in pts with advanced SS. Methods: Each substudy includes a dose confirmation stage to assess RP2D and a dose expansion stage. Key inclusion criteria are age ≥18 y; measurable disease per RECIST v1.1; HLA-A*02:01, A*02:05, or A*02:06 positivity; NY-ESO-1/LAGE-1a tumor expression; advanced (metastatic/unresectable) SS with t(X;18) translocation and anthracycline-based therapy receipt/completion/intolerance (SS only); and Stage IV NSCLC, receipt of ≥1 prior line(s) of standard of care (SOC) therapy including programmed death receptor- or ligand-1 inhibitors, and SOC chemotherapy receipt/intolerance (Substudy 1 only). Key exclusion criteria are prior malignancy that is not in complete remission or clinically significant systemic illness; prior receipt of gene/NY-ESO-1–specific therapy or allogenic stem cell/solid organ transplant; central nervous system metastases (SS only); and actionable genetic aberration and receipt/failure of ≥3 systemic therapy lines (Substudy 1 only). Primary endpoints are safety (adverse events) and tolerability (dose-limiting toxicities). Secondary endpoints include investigator-assessed overall response rate, duration of response, and maximum expansion/persistence and phenotype of infiltrating transduced T cells. Exploratory endpoints include laboratory parameters, overall survival, and anti-GSK3901961 or -GSK3845097 titers as applicable. Analyses will be descriptive. The substudies are enrolling. Funding: GSK (209012; NCT04526509). Editorial support was provided by Eithne Maguire, PhD, of Fishawack Indicia, part of Fishawack Health; funded by GSK. Previously presented at AACR 2021 (CT219). Clinical trial information: NCT04526509.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS2661
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 6
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    A pilot trial of autologous tumor infiltrating lymphocytes (lifileucel, LN-144) for patients with asymptomatic melanoma brain metastases.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS9606-TPS9606
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. TPS9606-TPS9606
    Abstract: TPS9606 Background: Melanoma brain metastases (MBM) are a leading cause of morbidity and mortality for patients with advanced melanoma. Modern systemic therapies are insufficient at controlling MBM, and median overall survival (OS) for pts with MBM is 〈 1 year. Adoptive T cell therapy using tumor infiltrating lymphocytes (TIL) has demonstrated efficacy in advanced melanoma. Lifileucel (LN-144), an autologous TIL product, was recently shown to be safe and effective for patient with PD-1 refractory melanoma. Patients with active MBM were excluded from lifileucel trials to date. Methods: This single-center pilot trial (NCT05640193) is enrolling up to 10 pts with asymptomatic MBM from non-uveal melanoma to receive lifileucel. Patients must have ≥1 intracranial lesion measuring 5-30mm visible on MRI to be used as a target lesion for modified (m)RECIST measurement, progression on prior anti-PD-1 therapy (with or without anti-CTLA-4), progression on targeted therapy if BRAF V600E/K-mutated), ECOG PS ≤1, ≥1 resectable lesion(s) (≥1.5 cm), recovered from prior surgery/anticancer treatment-related AEs (grade ≤1). Patients are not eligible if they have symptomatic MBM and/or require corticosteroids of ≥10 mg/day of prednisone or equivalent. Lifileucel is generated from resected tumor in a centralized GMP process. The regimen includes nonmyeloablative lymphodepletion, lifileucel infusion, and a short course of high-dose IL-2. The primary endpoint is feasibility, defined as ≥7/10 patients who undergo tumor harvest receiving lifileucel infusion. Secondary endpoints are safety, feasibility of manufacturing lifileucel in patients with MBM, and brain metastasis response rate (BMRR) per mRECIST 1.1. Exploratory endpoints include overall objective response rate by mRECIST 1.1, best extracranial response rate, intracranial progression-free survival (PFS), overall PFS, OS. Extensive correlative analyses of peripheral blood mononuclear cells, plasma, tumors, and cerebrospinal fluid are planned to better understand MBM growth, treatment resistance, and response of the central nervous system to lifileucel. Clinical trial information: NCT05640193 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.TPS9606
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 7
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    Acquired resistance to PD-1 blockade in NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9621-9621
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9621-9621
    Abstract: 9621 Background: Although durability is the trademark characteristic of response to PD-1 blockade, acquired resistance can occur. The frequency, patterns, and survival outcomes of patients with acquired resistance to PD-1 blockade are unknown. Methods: All patients with NSCLC treated with PD-1 blockade at MSKCC were examined. Acquired resistance was defined as initial CR/PR (by RECIST) followed by progression/death. Oligo vs systemic patterns of acquired resistance were defined as progression in ≤ 2 sites of disease or ≥ 3 sites of disease, respectively. Results: Of 1201 patients treated with PD-1 blockade, 243 (20%) achieved initial response and 189 (78%, 95% CI 72-83%) eventually developed acquired resistance (AR). Onset of AR was variable and decreased with longer duration of response (53% within 1 year, 37% 1-2 years, 10% 〉 2 years). Patients with PD-L1 expression 〈 50% and TMB 〈 8mut/Mb were more likely to develop resistance compared those with PD-L1 expression ≥50% and TMB ≥8mut/Mb (OR 5.5, p = 0.02). Unlike organ sites of primary refractory disease, AR commonly occurred in lymph nodes (41%) and infrequently in the liver (6%). Patterns of AR were most commonly oligo rather than systemic (79/141 [56%], 39/141 [28%] ); some patients died without radiographic progression (23/141 [16%]). Oligo-AR occurred later (median onset 13 vs 5.6 mo) and associated with improved post-progression survival (median OS 55.2 vs 9.2 mo, HR 6.0, p 〈 0.001) compared to systemic-AR. Post-progression survival was highest in patients with AR compared to those with initial SD or PD to PD-1 blockade (median 18.9 vs 12.5 vs 4.4, p 〈 0.001). Of 49 patients treated initially with locally-directed therapy for AR, 28 (57%) remain alive and systemic therapy-free. Conclusions: Acquired resistance to PD-1 blockade is common in NSCLC. Risk of acquired resistance is lower in biomarker-enriched patients and with increased duration of response. Patterns of acquired resistance is commonly oligo in nature, which is amenable to locally-directed therapy and can be associated with improved survival. Differences in organ-site distribution and post-progression survival suggest distinct biology associated with acquired resistance vs primary refractory disease.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9621
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 8
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    Long-term responders to PD-1 blockade in patients with advanced non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9549-9549
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9549-9549
    Abstract: 9549 Background: Long-term response – the plateau of the survival curve – is the transcendent benefit from PD-1 blockade. However, only a subset of responses achieve substantial durability. The frequency, characteristics, and predictors of long-term responders (LTR) to PD-1 blockade are not well known and may differ from short-term responders (STR). Methods: Patients with advanced NSCLC treated with anti-PD-1/PD-L1 therapy from two institutions (MSK and DFCI) were examined. Responses were assessed by RECIST. LTR was defined as PR/CR lasting ≥ 24 months. STR was defined as PR/CR lasting 〈 12 months. Comparisons were also made to patients with progressive disease (PD). PD-L1 expression was assessed by IHC. TMB was assessed by targeted NGS; high TMB was defined as ≥ median of the cohort. A subset had detailed molecular profiling by MSK-IMPACT. Fisher’s exact and Mann-Whitney U tests were used to compare features, and the log-rank test was used to compare survival. Results: Of 2318 patients (MSK n = 1536, DFCI n = 782), 126 (5.4%, 95% CI 4.6-6.4%) achieved LTR, with similar rates in both cohorts. STR occurred in 139 (6%). Overall survival was longer in LTR compared to STR (median NR vs 19.6 months, HR 0.07, p 〈 0.001). LTR had deeper responses compared to STR (median best overall response -69% vs -46%, p 〈 0.001). Patients with LTR were younger ( 〈 65 years old) and had increased TMB (≥ median mut/Mb) compared to both STR and PD (p = 0.006, p = 0.03; p 〈 0.001, p 〈 0.001). The rate of LTR was enriched among patients with both high TMB/high PD-L1 compared to those with low TMB/low PD-L1 (9% vs 1%, OR 9.2, p 〈 0.001), while STR was similar in both groups (7% vs 6%). 2% of patients with sensitizing EGFR mutations (n = 243) achieved LTR. Loss of function variants in ARID1A (14% vs 2%), PTEN (8% vs 0%), and KEAP1 (12% vs 2%) were enriched in LTR compared to STR (p 〈 0.05 for each). Among patients with KRAS mutations, the rate of LTR was higher in those with co-mutation with TP53 compared to STK11 (11% vs 2%, p = 0.01). Conclusions: Long-term response (LTR, ongoing response ≥ 24 months) to PD-1 blockade is an uncommon but profound clinical outcome in metastatic lung cancers. Younger age and high TMB correlate with LTR; the combination of high TMB/high PD-L1 enriches for LTR but not STR. Features predicting long term response may be distinct from those predicting initial response.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9549
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Adverse Effects Associated With Proton Pump Inhibitors
    American Medical Association (AMA) ; 2016
    In:  JAMA Internal Medicine Vol. 176, No. 2 ( 2016-02-01), p. 172-
    Details
    In: JAMA Internal Medicine, American Medical Association (AMA), Vol. 176, No. 2 ( 2016-02-01), p. 172-
    Type of Medium: Online Resource
    ISSN: 2168-6106
    URL: Article
    DOI: 10.1001/jamainternmed.2015.7927
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2016
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  • 10
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    Outcomes of single-agent PD-(L)-1 versus combination with chemotherapy in patients with PD-L1-high (≥ 50%) lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 9052-9052
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9052-9052
    Abstract: 9052 Background: Single agent PD-(L)-1 blockade (IO) and PD-(L)-1 blockade combined with chemotherapy (ChemoIO) are both standard first-line treatments for patients with PD-L1-high (≥ 50%) metastatic non-small cell lung cancer (NSCLC). These regimens have not been compared prospectively, so comparative effectiveness is unclear. It is also unknown if clinical and molecular tumor characteristics differentially associate with benefit to IO vs ChemoIO in patients with NSCLC with high PD-L1 tumor expression. Methods: All patients with metastatic NSCLC treated with IO or ChemoIO at two institutions (Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Institute) were reviewed. Patients with EGFR or ALK alterations, PD-L1 expression 〈 50%, treated with IO or ChemoIO in 〉 1 st line setting were excluded. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the IO vs ChemoIO groups and association with clinical, pathologic, and molecular features was examined. To account for NGS panel differences, tumor mutational burden (TMB) values were harmonized using a z-score conversion as previously described (Vokes et al, 2019). Results: Of 639 patients with stage IV EGFR/ ALK wild-type NSCLC and PD-L1 ≥50% treated in the 1 st line setting, 504 received IO and 135 received ChemoIO. Baseline ECOG performance status (p = 0.3), median PD-L1 % (p 〉 0.9) and TMB (p = 0.2) were similar between the IO and ChemoIO groups. For patients receiving IO vs ChemoIO, there was no significant difference in OS (HR 0.8, 95% CI 0.6 to 1.08; p = 0.2). Median PFS was shorter (HR 0.7, 95% CI 0.6 to 0.9; p = 0.004) and ORR was lower (40% IO vs 55% ChemoIO, p = 0.002) in the IO group. Among patients with durable responses ( 〉 6 months), never smokers were less common in the IO group (6% vs 18%, p 〈 0.001), but there was no difference in PD-L1 expression, TMB, or mutational ( KRAS, STK11, or KEAP1) profile to suggest differential predictors of benefit to IO or ChemoIO. Conclusions: In patients with PD-L1 high NSCLC, there was no survival benefit associated with the addition of chemotherapy to IO. There were also no clear differences in PD-L1 expression or molecular features associated with durable response to IO vs ChemoIO. These findings have implications for treatment selection in this population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.9052
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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