GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Beyond Steroids: Immunosuppressants in Steroid-Refractory or Resistant Immune-Related Adverse Events
    Elsevier BV ; 2021
    In:  Journal of Thoracic Oncology Vol. 16, No. 10 ( 2021-10), p. 1759-1764
    Details
    In: Journal of Thoracic Oncology, Elsevier BV, Vol. 16, No. 10 ( 2021-10), p. 1759-1764
    Type of Medium: Online Resource
    ISSN: 1556-0864
    URL: Article
    DOI: 10.1016/j.jtho.2021.06.024
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2223437-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Beyond steroids: Immunosuppressants in steroid-refractory/resistant immune related adverse events.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 9092-9092
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 9092-9092
    Abstract: 9092 Background: The optimal management for immune related adverse events (irAEs) in patients who do not respond or become intolerant to steroids is unclear. Guidelines suggest additional immunosuppressants based on case reports and expert opinion. Methods: We examined patients with advanced lung cancers at MSK treated with immune checkpoint blockade (ICB) from 2011-2020. Pharmacy records were queried to identify patients who received systemic steroids as well as an additional immunosuppressant (eg TNFα inhibitor, mycophenolate mofetil). Patient records were manually reviewed to examine baseline characteristics, management, and outcomes. Results: Among 2,750 patients with lung cancers treated with ICB, 51 (2%) received both steroids and an additional immunosuppressant for a severe irAE (TNFα inhibitor (73%), mycophenolate mofetil (20%)). The most common events were colitis (53%), pneumonitis (20%), hepatitis (12%), and neuromuscular (10%). At 90 days after start of an additional immunosuppressant, 57% were improved from their irAE, 18% were unchanged, and 25% were deceased. Improvement was more common in hepatitis (5/6) and colitis (18/27) but less common in neuromuscular (1/5) and pneumonitis (3/10). All patients with hepatitis received mycophenolate mofetil 500-1000mg BID for a median of 3 months, range 2-5 months. Of the 18 patients with colitis who improved with a TNFα inhibitor, 10 needed just one dose. Of 13 patients who died, 4 were related to toxicity from immunosuppression (3, infection-related deaths; 1, drug-induced liver injury leading to acute liver failure). Those who died from immunosuppressive therapy received higher amounts of systemic steroids than those who did not (max median 525 vs 132 mg prednisone equivalent, Mann Whitney U p = 0.004, total median 5.9k vs 2.3k mg prednisone equivalent, p = 0.004). Of 31 patients who received at least 3 weeks of prednisone ≥ 20mg, most (90%, 28/31) had at least one side effect that was brought to clinical attention (most commonly altered mood/ sleep, 52%, increase in BMI 〉 1kg/m2, 45%, and infection, 32%). Conclusions: Steroid-refractory/resistant immune related adverse events are rare. While existing treatments help patients with hepatitis and colitis, most patients with other irAEs remain refractory and/or experience toxicities from immunosuppression. Systemic steroid use likely contributed to side effects and mortality. A more precise understanding of the pathophysiology of specific irAEs is needed to guide biologically informed treatment regimens for severe irAEs to realize the true benefit of ICB therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.9092
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Molecular subtypes and clinical outcomes to initial systemic treatment in patients with small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9018-9018
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9018-9018
    Abstract: 9018 Background: Investigators have proposed that differential expression of the transcription regulators ASCL1 and NeuroD1 can be used to define molecular subtypes of small cell lung cancers (SCLCs). Here we evaluate SCLC subtypes based on ASCL1 and NeuroD1 expression in patients (pts) treated with first-line (1L) chemotherapy profiled with targeted next-generation sequencing (NGS). Methods: We used NGS (MSK-IMPACT) to profile tumors from pts with SCLCs. We performed IHC to assess ASCL1 (A) or NeuroD1 (N). Objective response rate (ORR) to therapy was determined using RECIST. PFS and OS were analyzed using Kaplan-Meier. Results: 281 pts with SCLCs were profiled with NGS (102 LS-SCLC; 179 ES-SCLC). Most frequently mutated genes were TP53 (90%), RB1 (68%), KMT2D (22%), NOTCH1 (15%), FAT1 (14%), PTPRD (12%). Mutations in BIRC3, FOXL2, TENT5C, TET1, NRAS, KIT, TSHR, ESR1 were enriched in ASCL1-/NeuroD1+ (A-/N+), and mutations in KMT2D and EP300 were enriched in A-/N- (p 〈 0.05). Copy number alterations in WWTR1, ATR, IKZF1, PALB2, PIK3CB were enriched in A-/N+ (p 〈 0.05). IHC for ASCL1 and NeuroD1 was performed on 78 samples: 11 A-/N-, 32 A+/N-, 4 A-/N+, 31 A+/N+. Overall survival at 1 year based on subtype was 25% in A-/N- (2/9), 60% in A-/N+ or A+/N- (13/32), and 55% in A+/N+ (10/25). For the 10 pts who survived 2 years, 5 were A+/N- and 5 were A+/N+. 146 pts treated with 1L platinum had RECIST-evaluable disease. ORR was 75% (110/146; 95% CI 68-82%). Median PFS was 7 months with CR/PR and 3.5 months with SD/PD (HR 0.32; 95% CI 0.18-0.56). Median OS was 17 months with CR/PR and 11 months with SD/PD (HR 0.55; 95% CI 0.34-0.9). Mutations in RUNX1, EPHA7, CDKN2A, FLT1 and copy number alterations in FGFR1, CCND1 were enriched in patients with SD/PD (p 〈 0.05). PFS rate at 6 months was 25% in A-N- (1/4), 60% in A-/N+ or A+/N- (9/15), and 55% in A+/N+ (6/11). For the 7 pts who survived 2 years, 3 were A+/N- and 4 were A+/N+. Conclusions: Molecular subtypes defined by ASCL1 and NeuroD1 encompass molecular characteristics that may predict patient outcomes. Further investigation is needed to delineate the underlying biological differences among the various subtypes to help define therapeutic vulnerabilities of each subtype of SCLC. Completion of IHC for ASCL1, NeuroD1 and additional key transcription factors POU2F3 and YAP1 are in progress for the entire cohort. WES and RNA sequencing are occurring in parallel and will be correlated with IHC results and clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9018
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    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
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Determination of clinical benefit among patients with radiological stable disease to immune checkpoint inhibitors.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 9041-9041
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 9041-9041
    Abstract: 9041 Background: SD is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs) and likely represents a heterogenous mix of responders and non-responders. This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. The ability to distinguish whom among patients with SD is actually benefiting from treatment would facilitate drug development and improve precision in correlative research. Methods: A systematic review was performed to characterize SD in ICI trials. SD and objective response was compared to proliferation index using TCGA gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of NSCLC treated with ICIs and had RECIST assessment. In patients with best overall response (BOR) of SD, serial cutpoints of two variables, % BOR and PFS, were tested to define a subgroup with similar survival as PR-minor (patients with partial response [PR] and % shrinkage 〈 median among responders). Results were then tested in two external validation cohorts (n = 326, n = 381). Results: Among trials of ICIs (59 studies, 14,280 patients), SD ranged from 16-42% in different tumor types and was associated with disease-specific proliferation index (Spearman rho = -0.75, p = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of 1220 patients with NSCLC who were treated with ICIs, 26% had SD, 19% had PR/CR, and 55% had PD. Outcomes among those with SD ranged widely (OS range 0.5-76 months, PFS range 0.2-49 months). The subset of SD with PFS 〉 6 months and no tumor growth mirrored PR-minor (OS HR 1.0) and was proposed as the definition of “SD-responder”. SD-responders (n = 87) represented 7% (95% CI 6-9%) of the overall population and 28% (95% CI 23-33%) of the SD population. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab. Conclusions: RECIST-defined SD to immunotherapy is common, heterogenous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS 〉 6 months and no tumor growth (̃1/3 of SD) may be considered “SD responders.” This definition may improve the efficiency of and insight derivable from clinical and translational research.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.9041
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract IA04: COVID-19 in patients with lung cancers in New York City
    American Association for Cancer Research (AACR) ; 2020
    In:  Clinical Cancer Research Vol. 26, No. 18_Supplement ( 2020-09-15), p. IA04-IA04
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 18_Supplement ( 2020-09-15), p. IA04-IA04
    Abstract: Background: Patients with lung cancers may have distinct vulnerability to severe COVID-19. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. A key question is whether PD-1 blockade therapy impacts COVID-19 severity. Methods: We identified consecutive patients with lung cancer and a positive SARS-CoV-2 RT-PCR test seen at a single cancer center in New York City. We performed detailed manual review of the disease course, medical and oncologic history. COVID-19 severity outcomes were predefined, including need for hospitalization, ICU/intubation/transition to DNI-status, or death. We examined clinical features associated with severity using single and multivariable analyses. Regarding the impact of PD-1 blockade, we prespecified several bio-plausible comparisons of PD-1 exposure. HLA alleles were inferred from NGS and compared to controls with lung cancer and no known COVID-19. Results: We identified 102 patients with lung cancers and a SARS-CoV-2 positive swab between March 12, 2020 and May 6, 2020. Patients were followed until May 11, 2020. COVID-19 was severe in patients with lung cancers (62% hospitalized, 25% died), but accounted for only 11% of deaths among patients with lung cancer during the pandemic. Determinants of COVID-19 severity were largely patient specific, including smoking status and chronic obstructive pulmonary disease. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies, did not impact severity. Likelihood of severe COVID-19 was generally similar across HLA class I supertypes. We found no significant differences in the impact of PD-1 blockade on COVID-19 severity. Modest numerical increases in severity of COVID-19 associated with prior PD-1 blockade were diminished (Odds ratio 0.86-1.01) after adjusting for expected imbalances in prior smoking history. Most patients recovered from COVID-19, including 25% of patients initially requiring intubation. Conclusion: COVID-19 is associated with a high burden of severity in patients with lung cancers. Patient-specific features, rather than cancer-specific features or treatments, were the greatest determinants of severity. In particular, PD-1 blockade did not appear to impact severity of COVID-19 in patients with lung cancers. Citation Format: Jia Luo, Hira Rizvi, Isabel R. Preeshagul, Jacklynn V. Egger, David Hoyos, Chaitanya Bandlamudi, Mark T.A. Donoghue, Marta Łuksza, Benjamin D. Greenbaum, Jedd D. Wolchok, Mark G. Kris, Matthew D. Hellmann. COVID-19 in patients with lung cancers in New York City [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr IA04.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1557-3265.COVID-19-IA04
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...