An evaluation of administrative data linkage for measurement of real-world outcomes of large clinical panel sequencing for advanced solid tumors.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 283-283
Author(s):  
Ramy Saleh ◽  
Philippe L. Bedard ◽  
Paul Nguyen ◽  
Eoghan Ruadh Malone ◽  
Celeste Yu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Administrative Data ◽  
Real World ◽  
Short Interval ◽  
Common Disease ◽  
Advanced Solid Tumors ◽  
Vital Status ◽  
Treatment Matching ◽  
The Impact ◽  
Panel Sequencing

283 Background: There is limited real-world evidence of impact of large clinical panel sequencing on treatment-matching for patients with advanced solid tumors. The province of Ontario has a single payer, publicly funded health care system. We linked genomic testing results from a prospective province-wide trial, OCTANE (Ontario-Wide Cancer TArgeted Nucleic Acid Evaluation), to administrative data to determine the feasibility of this approach for evaluating survival and the impact of sequencing on treatment matching. Methods: We linked all Ontario patients from Princess Margaret (PM) with panel testing results (tumor-only 555-gene panel) to province-wide administrative data on treatments and outcomes. Patients were recruited from August 2016 to August 2018. Only clinically actionable variants based upon OncoKB annotation (Level 1 and 2) were assessed for genotype-informed treatment matching. Results: All 888 eligible patients were successfully linked to administrative data. Mean age was 58 (±13) years, 635 (71.5%) were female. Most common disease sites were ovary (26.4%), uterus (14.0%), colorectal (11.8%) and breast (9.5%). Administrative data vital status was more complete than trial collected data with 262 of 476 deaths only recorded in administrative data. Median survival was 1.70 years (95% confidence interval 1.50-1.91). 247 (27.8%) had actionable mutations, most commonly PIK3CA (54.7%), BRCA1 (15.8%), BRCA2 (15.0%) and BRAF (8.9%). 37 (15.0%) and 42 (17.0%) patients with actionable mutations received targeted therapy within 6 and 12 months of test report date, respectively. Conclusions: This is the first known feasibility study of linked administrative data to measure outcomes of large clinical panel sequencing for patients with advanced solid tumors. Vital status was more complete with administrative data compared to trial-collected data, and treatment data was successfully linked. About one in twenty-one enrolled patients received genome-informed treatments within 12 months, or about one in six of all patients with actionable mutations. This may be due to short interval follow up, trial and drug access, successful standard of care treatments, early patient deterioration or limited alterations covered by the panel, among other causes.

An evaluation of administrative data linkage for measurement of real-world outcomes of large clinical panel sequencing for advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19303-e19303
Author(s):  
Ramy Saleh ◽  
Philippe L. Bedard ◽  
Paul Nguyen ◽  
Eoghan Ruadh Malone ◽  
Celeste Yu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Administrative Data ◽  
Real World ◽  
Short Interval ◽  
Common Disease ◽  
Advanced Solid Tumors ◽  
Vital Status ◽  
Treatment Matching ◽  
The Impact ◽  
Panel Sequencing

e19303 Background: There is limited real-world evidence of impact of large clinical panel sequencing on treatment-matching for patients with advanced solid tumors. The province of Ontario has a single payer, publicly funded health care system. We linked genomic testing results from a prospective province-wide trial, OCTANE (Ontario-Wide Cancer TArgeted Nucleic Acid Evaluation), to administrative data to determine the feasibility of this approach for evaluating survival and the impact of sequencing on treatment matching. Methods: We linked all Ontario patients from Princess Margaret (PM) with panel testing results (tumor-only 555-gene panel) to province-wide administrative data on treatments and outcomes. Patients were recruited from August 2016 to August 2018. Only clinically actionable variants based upon OncoKB annotation (Level 1 and 2) were assessed for genotype-informed treatment matching. Results: All 888 eligible patients were successfully linked to administrative data. Mean age was 58 (±13) years, 635 (71.5%) were female. Most common disease sites were ovary (26.4%), uterus (14.0%), colorectal (11.8%) and breast (9.5%). Administrative data vital status was more complete than trial collected data with 262 of 476 deaths only recorded in administrative data. Median survival was 1.70 years (95% confidence interval 1.50-1.91). 247 (27.8%) had actionable mutations, most commonly PIK3CA (54.7%), BRCA1 (15.8%), BRCA2 (15.0%) and BRAF (8.9%). 37 (15.0%) and 42 (17.0%) patients with actionable mutations received targeted therapy within 6 and 12 months of test report date, respectively. Conclusions: This is the first known feasibility study of linked administrative data to measure outcomes of large clinical panel sequencing for patients with advanced solid tumors. Vital status was more complete with administrative data compared to trial-collected data, and treatment data was successfully linked. About one in twenty-one enrolled patients received genome-informed treatments within 12 months, or about one in six of all patients with actionable mutations. This may be due to short interval follow up, trial and drug access, successful standard of care treatments, early patient deterioration or limited alterations covered by the panel, among other causes.

Prognostic value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with advanced solid tumors treated with PD-1 inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14132-e14132
Author(s):  
Miguel Gonzalez Velez ◽  
Giselle Alexandra Suero-Abreu ◽  
Marshall McKenna ◽  
Camille Michelle Johnson ◽  
Martin Gutierrez
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Prognostic Markers ◽  
Advanced Solid Tumors ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Platelet Lymphocyte Ratio ◽  
Longitudinal Response ◽  
Landmark Analyses ◽  
The Impact

e14132 Background: The use of PD-1 inhibitors (PD1) has been limited due to the lack of prognostic markers of response. Previous studies have suggested that indirect inflammatory markers such as neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) may correlate with response to treatment and improved survival. We sought to evaluate the impact NLR and PLR in a real world cohort of patients (pts) with advanced solid tumors treated with PD1. Methods: Records of all pts treated with PD1 between 2011-2017 at the John Theurer Cancer Center were reviewed. NLR and PLR were registered at baseline and longitudinally. We dichotomized as low (lNLR/lPLR), and high (hNLR ≥5/hPLR ≥160). Univariate logistic regression and Cox proportional hazards were used for progression free survival (PFS), and overall survival (OS). Landmark analyses were performed at cycles 2 (C2), and 5 (C5). Results: 178 pts received 1131 cycles of PD1. Median age was 65 (range 24-93); 43% were female. ECOG was ≥1 for 85%. 142 pts (80%), and 89 (50%) received ≥2C and ≥5C respectively. In univariate analyses, baseline hNLR and hPLR were independently associated with inferior OS (median 7.8 vs 18.3 months; HR 1.77, 95% CI 1.21-2.43; p = 0.004), ) and (median 6.4 vs 15.6 months; HR 1.42, 95% CI 1.09-2; p = 0.04) respectively. On landmark analyses, lNLR and lPLR were associated with longer PFS and OS at 2C, and 5C. Longitudinally, lNLR and lPLR correlated with response rate; NLR decreased by 0.08 (95% CI: -0.19 to -0.04; p = 0.03) and PLR by 17 (95% CI: -29 to -14; p = 0.07) per month in responders compared with non-responders. hNLR or hPLR did not correlate with increase in autoimmune toxicities. Conclusions: hNLR, hPLR are adversely prognostic markers in pts receiving PD1 inhibitors in a “real world cohort”. These markers correlate with a longitudinal response and may help predict response. Further prospective studies are needed to determine their utility in decision making during treatment.

scholarly journals The Impact of Anemia in Advanced Solid Tumors Treated with Sorafenib (SO) and Sunitinib (SU): A Pooled Analysis of 6 Trials

2012 ◽  
Vol 23 ◽  
pp. ix519
Author(s):  
S. Barni ◽  
K.F. Borgonovo ◽  
M. Ghilardi ◽  
M. Cabiddu ◽  
F. Maspero ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Pooled Analysis ◽  
Advanced Solid Tumors ◽  
The Impact

scholarly journals Thromboembolism in Patients with Advanced Solid Tumors Treated with Immunotherapy Compared with Platinum-Based Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1057-1057
Author(s):  
Satish Maharaj ◽  
Ruobing Xue ◽  
Anuja Abhyankar ◽  
Simone M Chang ◽  
Rebecca A. Redman ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Cumulative Incidence ◽  
Stage Iv ◽  
Stage Iii ◽  
Advanced Solid Tumors ◽  
Durable Response ◽  
Vein Thrombosis ◽  
Platinum Based Chemotherapy

Abstract Background: Venous and arterial thromboembolism (VTE/ATE) in patients with cancer are a significant cause of morbidity and mortality. Platinum-based chemotherapy (Platinum) has been associated with increased risk of VTE and ATE. In the last decade immunotherapy (IO) has emerged as first line treatment for many patients, alone or in combination with Platinum. Immune checkpoint inhibition can lead to a systemic proinflammatory state with some suggesting an associated procoagulant effect. A systematic review of studies on IO in advanced cancer reported incidence of 2.7% VTE and 1.1% ATE (n=20,273, Solinas et al 2020), concluding ATE/VTE is relatively rare with IO. However, emerging real world data suggest a higher incidence of thrombosis than initially reported, and how VTE/ATE incidence compares with IO as compared with Platinum remains unknown. Methods: We conducted a retrospective cohort study of consecutive patients with advanced solid tumors including non-small cell lung cancer (NSCLC, unresectable Stage III or Stage IV), melanoma (Stage III or Stage IV) and gastrointestinal cancers (Stage IV) during the period 2014-2020 at the Brown Cancer Center. Patients with thrombophilia, anticoagulation use, >1 malignancy, and use of regimens without IO/Platinum were excluded. Treatments included IO, Platinum (cisplatin, carboplatin, oxaliplatin) or combined IO-Platinum. VTE was defined as deep vein thrombosis, pulmonary embolism or visceral vein thrombosis. ATE was defined as any arterial thromboembolic event including arterial stroke, myocardial infarction, peripheral arterial thrombosis and visceral arterial thromboses. The primary outcomes of the study were cumulative incidence rates of VTE and ATE with events recorded in time from diagnosis. Cumulative incidence analyses were performed to compare rates of VTE and ATE for the different modalities of treatment (IO, IO-Platinum, Platinum). Results: A total of 357 patients were included. Clinical characteristics are presented in Table 1 - just over half were male, median age 59 yrs and predominant history of smoking. NSCLC was most represented (41%) followed by GI cancer (34%) and melanoma (25%). Treatment modalities were fairly distributed : IO (34%), IO-Platinum (30%) and Platinum (36%). Over a median follow up of 2.5 yrs, VTE occurred in 80 patients (22%), most commonly PE followed by DVT and VVT (Table 2). At median follow up, the cumulative incidence of VTE with IO was 15.1% [95% CI (9.3-24.6)] vs. IO-Platinum at 23.2% [95% CI (15.1-35.7)] and Platinum at 29.2% [95% CI (21.7-39.4)]. ATE occurred in 25 patients overall (7%) (Table 2). At median follow up, cumulative incidence of ATE with IO was 3.3% [95% CI (1.3-8.7)] vs. IO-Platinum at 7.0% [95% CI (2.5-19.4)] and Platinum at 9.9% [95% CI (5.6-17.6)]. Cumulative incidence frequencies for VTE/ATE are presented graphically according to each treatment modality (Figure). Conclusion: In this cohort of patients, increased incidence of VTE/ATE over time was seen following immunotherapy alone or combined with platinum-based chemotherapy. Immunotherapy can induce a durable response with unprecedented survival benefits and patients with advanced solid tumors are at risk for increasingly longer periods. The reasons behind increased real world incidence relative to historical adverse event reporting are likely multifactorial and further research in larger cohorts is needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Comprehensive genomic profiling of 30,000 consecutive solid tumors

2020 ◽  
Author(s):  
Scott A. Tomlins ◽  
Daniel H. Hovelson ◽  
Jennifer M. Suga ◽  
Daniel M. Anderson ◽  
Han A. Koh ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Tumor Tissue ◽  
Tissue Sample ◽  
Treatment Selection ◽  
Genomic Profiling ◽  
Tissue Samples ◽  
Comprehensive Genomic Profiling ◽  
Prostate Carcinomas ◽  
The Impact

AbstractPurposeTissue-based comprehensive genomic profiling (CGP) is increasingly utilized for treatment selection in patients with advanced solid tumors, however real-world tissue availability may limit widespread implementation. Here we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples.Patients and MethodPost-hoc, non-prespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex PCR based-CGP (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Tumor tissue sample characteristics and PCR-CGP performance were assessed across all tested tumor samples, including exception samples not meeting minimum input requirements (<20% tumor content [TC], <2mm2 tumor surface area [TSA], DNA or RNA yield <1ng/ul, or specimen age >5yrs). Tests reporting at least one prioritized alteration or meeting all sequencing QC metrics (and ≥20% TC) were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting at least one actionable/informative alteration or those meeting all sequencing QC metrics (and ≥20% TC) were considered actionable.ResultsPCR-CGP was attempted in 31,165 of 32,048 (97.2%) consecutively received solid tumor tissue samples. Among the 31,165 tested samples, 10.7% had low (<20%) tumor content (TC) and 58.4% were small (<25mm2 TSA), highlighting the challenging nature of samples received for CGP. Of the 31,101 samples evaluable for input requirements, 8,079 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.6% of exception samples. Importantly, 80.6% of 1,344 tested prostate carcinomas and 87.8% of 1,144 tested lung adenocarcinomas yielded results informing treatment selection.ConclusionMost real-world tumor tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for >94% of samples, potentially expanding the proportion of CGP-testable patients, and thus the impact of biomarker-guided targeted and immunotherapies.

Safety and tolerability of MEDI0562 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3003-3003
Author(s):  
Jonathan Wade Goldman ◽  
Sarina Anne Piha-Paul ◽  
Brendan D. Curti ◽  
Katrina Pedersen ◽  
Todd Michael Bauer ◽  
...  
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Memory T Cells ◽  
Phase 1 ◽  
Evaluation Criteria ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
The Impact

3003 Background: We report safety and tolerability of MEDI0562, a humanized IgG1κ OX40 monoclonal antibody (mAb), in combination with durvalumab (durva; anti-PD-L1 mAb) or tremelimumab (treme; anti-CTLA-4 mAb) in patients (pts) with previously treated advanced solid tumors. Methods: In this phase 1, open-label study (NCT02705482), adult pts received escalating doses of MEDI0562 (2.25, 7.5 or 22.5 mg/kg) every 2 wks (Q2W) in combination with durva (1500 mg/kg) or treme (75 or 225 mg/kg) Q4W, until confirmed disease progression or unacceptable toxicity. Tumor assessments were performed Q8W with immune-related Response Evaluation Criteria in Solid Tumors. Results: In total, 27 and 31 pts received MEDI0562 + durva or treme, across 5 dose combination cohorts (3 + 3 design), with a maximum tolerated dose of 7.5 mg MEDI0652 + 1500 mg durva and maximum administered dose of 10 mg MEDI0562 + 225 mg treme. Median duration of exposure was 12.0 (range 2.0–80.9) and 8.0 (range 2.0–42.0) wks, respectively. Two (22.5 mg MEDI10562 + durva) and 3 (2.25 mg MEDI0652 + 225 mg treme, 22.5 mg MEDI0562 + 75 and 225 mg treme) dose limiting toxicities were observed. For MEDI0562 + durva and MEDI0562 + treme groups respectively, treatment-emergent adverse events (TEAEs) were reported in 96.3% and 100% of pts; most common TEAEs were fatigue (55.6%) and pruritus (45.2%), Gr 3/4 TEAEs occurred in 74.1% and 67.7%; and MEDI0562-related AEs were reported in 20 (74.1%) and 24 (77.4%) pts. Six TEAEs in each group led to MEDI0562 discontinuation (22.2% and 19.4%, respectively), 2 led to death (renal failure [7.5 mg MEDI0562 + durva], multiple organ dysfunction syndrome [22.5 mg MEDI0562 + 225 mg treme]). Three response evaluable pts had PR (11.5% [7.5 and 22.5 mg MEDI0562 + durva, n = 26]). Median overall survival was 17.4 and 11.9 mos for MEDI0562 + durva and MEDI0562 + treme, with stable disease seen in 9 pts from each group, 34.6% vs 29.0%, respectively. Serum exposure of MEDI0562 increased dose proportionally. Post treatment serum antidrug antibody (ADA) was detected in 20 pts from MEDI0562 + durva and MEDI0562 + treme (74.1% and 71.4%, respectively). The impact of ADA on MEDI0562 pharmacokinetics was seen at all doses. Mean percentage of Ki67+CD4+ and Ki67+CD8+ memory T cells increased, while mean percentage of OX40+CD4+ memory T cells decreased following the first dose of MEDI0562 + durva or treme. Conclusions: The safety profile of MEDI0562 in combination with durva or treme was similar between groups. Clinical activity was observed with MEDI0562 + durva in pts with advanced solid tumors. Clinical trial information: NCT02705482 .

Association of survival with chemotherapy intensity, myelosuppression, and supportive care in patients with advanced solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6534-6534 ◽  
Author(s):  
Gary H. Lyman ◽  
Marek S. Poniewierski ◽  
Adane Fekadu Wogu ◽  
Eva Culakova ◽  
Nicole Maria Kuderer ◽  
...  
Keyword(s):  
Supportive Care ◽  
Solid Tumors ◽  
Advanced Cancer ◽  
Absolute Risk ◽  
Phase 1 ◽  
Dose Intensity ◽  
Cancer Type ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
The Impact

6534 Background: The value of chemotherapy and supportive care for advanced cancer has been questioned. Two systematic reviews were conducted to study the impact of chemotherapy-induced myelosuppression and supportive care on subsequent survival. Methods: Phase 1 identified trials evaluating the relationship of chemotherapy associated with myelosuppression and subsequent survival in patients with cancer. Phase 2 evaluated randomized controlled trials (RCTs) chemotherapy with or without G-CSF support for advanced cancer. Outcomes included hazard ratios (HR), relative risk (RR) and absolute risk (AR) ±95% CI. Results: In Phase 1, 11 of 25 identified studies were conducted in patients with advanced/metastatic disease with 10 in patients with solid tumors. Among the 7 studies in patients with solid tumors reporting survival outcomes, a consistent association between chemotherapy-associated myelosuppression and reduced mortality was observed (HR=0.69; 0.61-0.77; P<.0001). A significant interaction between myelosuppression and cancer type for mortality was observed (P=.046) with significant effects observed for all tumor types. In Phase 2, 22 of 61 RCTs identified were in patients with stage IV solid tumors. Mortality was reduced with chemotherapy with G-CSF support overall (RR=0.95; 0.92-0.98; P=.003) and in patients with non-small cell lung cancer (RR=0.90; P=.037; AR=-6.6%; P=.014), sarcomas (RR=0.73; P=.007; AR=-22.1%; P=.004) or urothelial cancers (RR=0.87; P=.019; AR=-11.4%; P=.016). Reductions in mortality were seen with dose dense chemotherapy (RR=0.88; P=.021; AR=-10.0%; P=.019) and when survival was the primary outcome (n=11;RR=0.92; P=.022; AR=-5.2%; P=.001) with a trend toward greater benefit with longer duration of follow-up (P=.071). Conclusions: Studies of patients with advanced solid tumors demonstrate favorable effects of chemotherapy effect on survival. Chemotherapy treatment resulting in myelosuppression is associated with reduced mortality. RCTs of patients with advanced/metastatic solid tumors confirm that greater chemotherapy dose intensity with G-CSF support is associated with greater reductions in mortality.

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