tbuckley/cabot-search huggingface dataset:
Risk of not receiving 2<sup>nd</sup> line therapy is high in EGFR mt+ pts: Real world data of certified lung cancer centers on treatment sequence in EGFR mt+ pts.
Authors: Julia Roeper, Markus Falk, Markus Tiemann, Claas Wesseler, Gunther Wiest, Sandra Sackmann, Dieter Ukena, Lukas Heukamp, Frank Griesinger
Journal: Journal of Clinical Oncology (2018)

e21220 Background: Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI's. The number of pts switching from 1st gen. to 3rd gen. TKI (30%) appeared to be low and it is questionable whether these data represent real world sequencing treatment patterns. Therefore, we investigated the sequence pattern, i.e. the percentage of 2nd line therapy in EGFR mt+ pts in 3 lung cancer centers in Germany. Methods: Data of 912/1477 pts tested for EGFR mt+ were analyzed between 2009-2017. 140/144 patients with an activating EGFR mutation (16%) and treated with systemic therapy (4 pts received no therapy) were identified and their treatments were captured as well as their outcome. 36 pts were treated before accessibility to 3rd gen. TKI and 104 pts after accessibility to 3rd gen. TKI. Results: 130/140 pts were treated with 1st line TKI and 10 received 1st line chemotherapy. 17 pts are still on 1st line TKI, 8 pts were lost to follow-up, 3 pts died while on 1st line TKI. 112 pts were candidates for 2nd line therapy. 34/112 (30%) of these pts did not receive 2nd line therapy. Causes for not receiving 2nd line therapy were pts refusal (n = 2), bad PS (n = 26) frequently due to CNS metastases, fast progression and death (n = 6). After accessibility of 3rd gen. TKI, 20 of 66 (30%) pts did not receive 2nd line therapy. Median OS of the overall cohort was 27 months (n = 140), median OS of pts receiving 2nd line (n = 78) vs. no 2nd line (n = 62) was 36 vs. 14 months (p < 0.0001). After accessibility of 3rd gen. TKI 30/104 pts (29%) receive a 3rd gen. TKI after 1st line or 2nd line therapy. Median OS of pts receiving (n = 30) and not receiving 3rd gen. TKI (n = 110) was 55 months vs. 22 months (p < 0.0001). Conclusions: In real world, a significant number of pts treated with 1st or 2nd gen. TKI do not reach 2nd line therapy even when 3rd gen. TKI were accessible. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS and lack of possibility to test for T790M in the minority of cases (n = 28/66, 42% not tested). These data, although favorable for the small and very selected cohort of pts treated with Osimertinib, might argue for the most effective therapy in 1st line for pts with EGFR mt+ tumors.
Prevention of Lyme Disease after Tick Bites
Authors: David Magid, Brian Schwartz, Joseph Craft, J. Sanford Schwartz
Journal: New England Journal of Medicine (1992)

In areas of endemic disease, the probability of Lyme disease after a tick bite ranges from about 0.012 to 0.05. Early treatment with oral antibiotics prevents most complications of Lyme disease, but antibiotics are generally not prescribed until rash or other symptoms develop.
Associations of age, PD-L1 status, BRAF mutation and tumor mutational burden (TMB) in advanced melanoma.
Authors: Geoffrey Thomas Gibney, Shaojun Tang, Kelsey Poorman, Anthony J. Olszanski, Burton Larry Eisenberg, Inderjit Mehmi, Jeffrey M. Farma, Gino Kim In, Asim Amin, Suthee Rapisuwon, Ari M. Vanderwalde, Michael B. Atkins
Journal: Journal of Clinical Oncology (2018)

e21609 Background: Combined immune checkpoint inhibition (ICI) has demonstrated improved survival in patients (pts) with advanced melanoma. Several factors have been associated with greater benefit with combination vs monotherapy, including presence of BRAF V600 mutation, low PD-L1 expression, and age ≤65. However, the association with TMB, a predictive biomarker in other ICI studies, remains unclear. We sought to determine associations of these variables in advanced melanoma. Methods: A total of 675 melanomas were molecularly profiled at Caris Life Sciences and analyzed for age, PD-L1 status (SP142; ≥5%), BRAF mutation (BRAF V600E/K), and TMB-H (≥17mut/mb). Non-BRAF V600E/K tumors were considered wild-type (WT). Sequencing was performed using a targeted panel on Illumina NextSeq platform. Association analyses were performed with Cramer's V test. Results: Within the cohort, 50% were age ≤65yrs, 24% PD-L1+, 33% BRAF mutant, and 39% TMB-H. Co-occurrence of PD-L1+ and TMB-H was 11%. For BRAF mutants, TMB-H showed positive association with age ≥65yrs (p = 0.0002); a similar trend was seen in BRAF WT. Interestingly, there was no significant association between PD-L1+ and either BRAF status or age. BRAF mutation was associated with age < 65 (p = 0e+00) and TMB < 17 (p = 0.0002). In BRAF WT tumors, the significant association between TMB and PD-L1 status or age was maintained. However, in BRAF mutant tumors, TMB was associated with age, but not PD-L1 status (p = 0.82). Tumor infiltrating lymphocyte (TIL) density will be assessed to clarify differences based on BRAF status and PD-L1. Conclusions: The strong association between TMB and PD-L1 status in BRAF WT tumors may represent a subgroup highly responsive to ICI. The lack of association between TMB and PD-L1 in BRAF mutant tumors suggests other factors may contribute to immune evasion. These finding may be influential in considering candidates for ICI monotherapy versus combination therapy. While the associations among age, TMB, and BRAF status are consistent with past studies, further studies are warranted for validation of novel findings. All Patients BRAF WT BRAF V600E/K Age ≤65yrs 49% 42% 63% ≥ 65yrs 50% 57% 36% PD-L1 < 5% 75% 75% 75% > 5% 24% 24% 24% TMB ≤17 61% 56% 71% ≥17 38% 43% 28%
Prevalence of Hodgkin lymphoma and relapsed or refractory Hodgkin lymphoma in the US.
Authors: Melissa Lingohr-Smith, Baiju Aurora, Jay Lin, Brandy Menges, Dinara Makenbaeva
Journal: Journal of Clinical Oncology (2016)

e19020 Background: Although most Hodgkin lymphoma (HL) patients respond to primary therapy, some patients experience relapses or are refractory to treatment (RR-HL) and have a poor prognosis. The objectives of this study were to investigate the prevalence of HL and RR-HL in the US, using data from a large healthcare claims database. Methods: Patients with ≥ 1 diagnosis for HL between 1/1/2013 and 9/30/2014 (prevalence estimate period) in the MarketScan Commercial and Medicare databases were identified. RR-HL patients were identified as any HL patient with ≥ 1 record for either an autologous stem cell transplant (ASCT) or brentuximab treatment between 1/1/2010 and 9/30/2014 (entire study period). Prevalence rates of HL and RR-HL were calculated as the number of patients with HL or RR-HL divided by the total number of persons with insurance enrollment between 1/1/2013 and 9/30/2014 in the MarketScan databases. Age- and sex-specific prevalence rates for HL and RR-HL were estimated. The estimated prevalence rates based on the database claims analysis and US national population estimates obtained from the US Census Bureau were used to project the prevalence of HL and RR-HL in the US population in 2014. Results: Of persons with any insurance enrollment in the MarketScan databases during the study period (N = 58,968,235), 24,812 (0.04%) were identified as having HL (mean age: 48.6 years) between 1/1/2013 and 9/30/2014. Of this HL population, 712 (2.87%) were identified as RR-HL patients, with 432 (1.74%) having received ASCT, 199 (0.80%) having received brentuximab, and 81 (0.33%) having received both ASCT and brentuximab treatments during the study period. According to the national projection using the US census population estimate, the overall number of persons with HL in the US is estimated at 149,615 in 2014, with 2.72% having RR-HL (Table). Conclusions: Among persons with HL the proportion with prior ASCT and/or brentuximab treatment estimated from a national healthcare claims database is approximately 3% of the HL population in the US. Estimated national prevalence of RR-HL among patients with HL. HL N = 149,615 (100%) ASCT without brentuximab 2,323 1.55% Brentuximab without ASCT 1,352 0.90% ASCT and brentuximab 402 0.27% Total (RR-HL) 4,077 2.72%
Tolerability of paclitaxel/carboplatin (PCb) in solid tumor patients (pts) infected with HIV.
Authors: Missak Haigentz, Page C. Moore, Lee Ratner, David H. Henry, Paul G. Rubinstein, Juan Carlos Ramos, Michelle A. Rudek, Yoko Eng, Timothy Patrick Cooley, John F. Deeken, Richard F. Little, Ronald T. Mitsuyasu
Journal: Journal of Clinical Oncology (2017)

e14077 Background: Although cancer has long been a recognized hallmark of the HIV epidemic, the preservation of immunologic health with modern antiretroviral therapy (ART) and aging has resulted in a population increasingly susceptible to cancers not traditionally associated with advancing immunosuppression. Several of these cancers (including lung, anal and head &amp; neck) are seen in excess compared to the background population. Defining tolerability of standard treatments and analyzing potential interactions between ART and chemotherapy provides evidence necessary to mitigate treatment disparities. Methods: We conducted a study to evaluate the tolerability of PCb in HIV+ cancer pts. AMC-078 (NCT01249443), originally designed as a phase I of vorinostat in combination with fixed doses of P (at 175mg/m 2 ) and Cb (AUC 6) every 3 weeks, was amended to study pts treated with PCb alone after phase III testing in the background population was negative for the combination in lung cancer. Eligibility criteria: PS ≤ 2, advanced solid tumor and normal organ function, including CD4 count &gt; 100 cells/mcL on stable ART. Up to 6 cycles of PCb were permitted. Clinically significant adverse events (AE) in prior cycles were managed by dose reductions. Results: 17 pts (10M/7F; median CD4, 389/mcL) were accrued, including lung (9) and anal (3) cancers; 8 pts had ritonavir (potent CYP inhibitor)-containing ART. 65 PCb cycles were administered to 16 evaluable pts, for a mean of 4+ cycles/pt; only 2 pts were treated with vorinostat. AE of special interest included ≥G3 (febrile) neutropenia and ≥ G2 neuropathy, below. 4 pts had partial responses (3 confirmed). Pharmacokinetic analyses (7 pts) are pending. Conclusions: PCb has similar toxicity profile in fit pts with HIV infection. No signal for worse myelosuppression or neuropathy was observed by ART regimen. Routine use of GCSF or empiric dose reduction for presumed risk is unjustified. Results support standard cancer treatment for this underserved population. Clinical trial information: NCT01249443. [Table: see text]
Association of venous thromboembolism with increased mortality in patients with multiple myeloma.
Authors: Martin W. Schoen, Suhong Luo, Brian Gage, Kenneth Robert Carson, Kristen Marie Sanfilippo
Journal: Journal of Clinical Oncology (2018)

8051 Background: Previous studies have demonstrated conflicting results regarding the effect of venous thromboembolism (VTE) on survival in patients with multiple myeloma (MM). In order to understand the impact of VTE on survival in MM, we studied outcomes in a nationwide population of United States Veterans with MM. Methods: Patients with newly diagnosed MM treated within the Veterans Health Administration (VHA) system between September 1, 1999 and 2013 were identified within the VHA Central Cancer Registry. Patients who did not receive treatment within 6 months of diagnosis were excluded. Age, sex, race, body mass index (BMI), co-morbidities, treatment (including transplant status), hemoglobin (HGB), albumin, and renal function were included. VTE was identified using an algorithm consisting of a combination of ICD-9 codes and VTE treatment. Cox proportional hazards regression modeling was used to assess the association between VTE as a time-varying exposure and overall survival while controlling for known prognostic factors. Results: The analytic cohort consisted of 4797 patients, of which 641 developed VTE after MM diagnosis (15.4%). After controlling for age, race, BMI, medical comorbidities, baseline lab characteristics, year of diagnosis, and initial treatment with a novel agent (thalidomide, lenalidomide, or bortezomib), patients with MM and VTE had an increased risk of death at 2 years (Hazard Ratio [HR] 1.28, 95% CI 1.09-1.52) and 5 years (HR 1.17, 95% CI 1.04-1.31) but not at one year (HR 1.15, 95% CI 0.90-1.49). Landmark analyses of patients surviving at least 6 months showed VTE continued to be a risk factor for death at 2 years (HR 1.23, 95% CI 1.05-1.45) and 5 years (HR 1.17, 95% CI 1.04-1.32). Conclusions: After controlling for known MM prognostic factors, VTE was significantly associated with increased mortality in the 2-years following MM diagnosis. Whether the observed increase in mortality is a direct result of VTE could not be determined in this study. Further study of MM patients with a high-risk for VTE, including studies of thromboprophylaxis, could clarify the significance of this association.
Correlation between re-biopsy site and detection of T790M mutation in NSCLC patients treated with EGFR TKI.
Authors: Fumie Shigematsu, Yoshihito Kogure, Hideo Saka, Arisa Yamada, Akane Ishida, Yuko Ise, Kazumi Hori, Saori Oka, Masashi Nakahata, Chiyoe Kitagawa, Masahide Oki
Journal: Journal of Clinical Oncology (2017)

e20620 Background: Re-biopsy is important to decide the treatment after EGFR-tyrosine kinase inhibitor (TKI) failure in non-small cell lung cancer (NSCLC) patients. We hypothesized that the T790M mutation in EGFR might show heterogeneity depending on the re-biopsy site. Methods: NSCLC patients who had received initial EGFR-TKI since January 2009 to December 2016, at any stage and recurrence after surgery and at any line of treatment, were included. Results: In total, 128 patients were included. Median age at EGFR-TKI therapy initiation was 73 (range, 38–97) years; 67% patients were female, all were Asian, 56% had never smoked, and 99% had adenocarcinoma. Of total 128 patients, 109 showed progressive disease. Median progression-free survival (PFS) was 10 (0.56–57) months. Median period since EGFR-TKI failure until the first re-biopsy was 197 (0–1322) days. Re-biopsy was performed 50 times in 42 patients; the number of T790M positive, negative, and pathologically negative patients was 20, 17, and 5, respectively, and the number of re-biopsies in these patients was 20, 22, and 8, respectively. Median PFS was longer in T790M positive patients than in negative patients significantly (17 [11–24] vs. 7.6 [4.3–11] months, P = 0.007). Characteristics such as gender, smoking status, proportion of stage IV, time between EGFR-TKI failure and first re-biopsy, and number of biopsies did not affect the T790M status in the biopsies. T790M positive group had more exon 19 deletions than negative group significantly (75% vs. 23%, P = 0.012). Biopsies at primary lesion, distant, and pleural effusion (PE) were 25% vs. 50%, 60% vs. 36%, and 15% vs. 14%, respectively, in the T790M positive vs. negative groups. Compared with the biopsy-site at diagnosis, the site was same as before in 35% vs. 50% cases (primary lesion [20% vs. 45%], distant [10% vs. 4.5%], and PE [5% vs. 0%]) and was new in 55% vs. 41% cases (distant lesions [45% vs. 27%] and PE [10% vs. 14%]) in the T790M positive vs. negative groups, respectively. Conclusions: In NSCLC patients treated with EGFR-TKI, re-biopsy was performed in distant lesions more frequently in the T790M positive cases than in negative cases. However, the T790M status was not correlated with the re-biopsy site.
Evaluation of an online tool providing management guidance for adverse events associated with immune checkpoint inhibitors.
Authors: Krista Marcello, Kevin Obholz, Kristen Rosenthal, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2017)

e18131 Background: Immune checkpoint inhibitors (ICIs) are altering the treatment paradigm in oncology; but many healthcare providers (HCPs) are still unfamiliar with ICIs and the unique associated immune-related adverse events (irAEs). An online tool was developed to give HCPs easy access to fair-balanced guidance and algorithms that extend beyond standard recommendations found in the respective product inserts. Methods: Tool users input patient symptoms, organ system affected, and the grade of the event along with their planned management strategy; they were then provided an expert recommendation to guide management of that specific irAE. Recommendations in the tool comprised algorithms developed from peer-reviewed studies and personal clinical experience of several experienced physicians. Case entries (collected from 11/9/16 through 1/17/17), variation of intended management with recommended management, and impact on practice were analyzed. Results: To date, 918 unique tool queries have been entered by HCPs. Cases of GI symptoms were most frequently (29% of all cases) entered into the tool (Table). The planned management of pulmonary- and endrocrine-related AEs differed from expert recommendations for the highest percentage of cases (53% and 65%, respectively). Overall, the intended management plans differed from expert recommendations in 49% of HCP tool queries. Most (93%) HCPs indicated that this online tool either changed their management plan or that their planned strategy was reinforced by using this tool. Conclusions: These data suggest that many HCPs are challenged to manage irAEs associated with ICIs and that an online tool can provide a resource to improve patient care and safety. A detailed analysis of the tool, including case entries and planned management vs expert recommendation for each irAE and grade will be presented. [Table: see text]
FOLFIRINOX until progression, FOLFIRINOX with maintenance treatment, or sequential treatment with gemcitabine and FOLFIRI.3 for first-line treatment of metastatic pancreatic cancer: A randomized phase II trial (PRODIGE 35-PANOPTIMOX).
Authors: Laetitia Dahan, Jean Marc Phelip, Karine Le Malicot, Nicolas Williet, Jérôme Desrame, Julien Volet, Caroline Petorin, David Malka, Christine Rebischung, Thomas Aparicio, Cedric Lecaille, Yves Rinaldi, Anthony Turpin, Anne Laure Bignon, Jean-Baptiste Bachet, Jean Francois Seitz, Come Lepage, Eric Francois
Journal: Journal of Clinical Oncology (2018)

4000 Background: Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis (5-year overall survival [OS] <5%). Our previous trial (PRODIGE4-ACCORD11) has demonstrated the superiority of 6-month [m] chemotherapy with FOLFIRINOX over gemcitabine in terms of progression-free survival [PFS] (6.4 vs. 3.3 m; HR: 0.47; 95%CI: 0.37-0.59; p<0.001) and OS (11.1 vs. 6.8 m; HR: 0.57; 95%CI: 0.45-0.73; p<0.001), at the expense of higher toxicity, notably cumulative, often limiting, peripheral neuropathy with oxaliplatin. In this randomized Phase II trial, we aimed to assess an oxaliplatin 'stop-and-go' strategy and an alternative sequential strategy in mPC. Methods: Patients (pts) were randomized to receive either 6m FOLFIRINOX (arm A), 4m FOLFIRINOX followed by LV5FU2 maintenance treatment for controlled pts, and treatment reintroduction at disease progression (arm B), or a sequential treatment alternating gemcitabine and FOLFIRI.3 every 2m (arm C). The primary endpoint was to evaluate the 6m-PFS rate (H0: 30%, H1: 45%, Fleming design) in order to select the best therapeutic strategy for a future Phase III clinical trial. Results: Between Jan 2015 and Nov 2016, 273 pts (mean age: 63 years; range: 40-76) were enrolled (A: 91; B: 92; C: 90). The median durations of treatment were 5.1, 6.2, and 4.4 m in A, B, and C respectively. Grade 3/4 neurotoxicity occurred in 10% of pts in arm A and 19% of pts in arm B. Median ratio of oxaliplatin was 83% in A and 92% in B. 6m-PFS rates were 47% in A, 44% in B, and 34% in C. 4m objective response rates were 35% in A, 41% in B, and 17% in C. Median PFS was respectively 6.3, 5.7 and 4.5 m in A, B and C. Median OS was 10.1 in A, 11.2 in B and 7.3 m in C. The median duration of first maintenance therapy in B was 3.3 m (range: 0.03-22.6). Conclusions: Maintenance with LV5FU2 appears to be feasible and effective in patients with mPC controlled after 4m of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity rate was higher in the maintenance therapy arm, likely because of higher cumulative oxaliplatin dose.1Conroy NEJM 2011. Clinical trial information: NCT02352337.
Clinical factors associated with urinary tract cancers (UTCs) among Lynch syndrome (LS) patients (Pts).
Authors: Jonathan W. Wischhusen, Chinedu I. Ukaegbu, Tara G. Dhingra, Hajime Uno, Fay Kastrinos, Sapna Syngal, Matthew B. Yurgelun
Journal: Journal of Clinical Oncology (2018)

1517 Background: LS is the one of the most common inherited causes of cancer and predisposes to a wide variety of cancers. UTCs (kidney, renal pelvis, ureter, and bladder cancer) are collectively the second- and fourth-most common LS-associated cancers in male and female LS pts, respectively. This study’s aim was to identify clinical factors associated with UTC among LS pts. Methods: The study population was a cohort of 52758 consecutively ascertained patients undergoing germline LS testing from 6/2006-7/2013 at a commercial laboratory. Clinical data, including age at genetic testing, personal history (PHx) of cancer, and family history of cancer in first- and second-degree relatives (FDRs and SDRs, respectively) were obtained from test request forms completed by the ordering provider. Multivariable logistic regression was performed to identify clinical factors associated with PHx of UTC among LS carriers. Results: Data from 51086 pts was analyzed after excluding 1672 pts without clinical data (N = 1664) or > 1 LS mutation (N = 8). Of these, 3828 carried pathogenic LS mutations (1346 MLH1, 1639 MSH2, 670 MSH6, 145 PMS2, and 28 EPCAM). 158/3828 (4.1%; 95% CI 3.5-4.8%) LS pts had a PHx of UTC (49 kidney; 62 ureter/renal pelvis; 67 bladder; 21 multiple UTCs) and 369 (9.6%; 95% CI 8.7-10.6%) had any family history of UTC. Compared to non-carriers, LS pts were significantly more likely to have a PHx of any UTC (4.1 vs 1.2%; P < 0.0001), kidney cancer (1.3% vs 0.7%; P = 0.0003), ureter/renal pelvis cancer (1.6% vs 0.1%; P < 0.0001), bladder cancer (1.8% vs 0.4%; P < 0.0001), and any family history of UTC (9.6% vs 6.5%; P < 0.0001). By multivariable logistic regression, PHx of UTC among LS pts was significantly associated with male sex (OR 2.04; 95% CI 1.73-2.41), age at genetic testing (OR 1.97 per 10 years; 95% CI 1.86-2.09), MSH2 mutation carriage (OR 4.03; 95% CI 3.29-4.94; ref: non-MSH2 LS mutations), and family history of UTC (OR 2.07 for each FDR/SDR with UTC; 95% CI 1.80-2.40). Conclusions: Increasing number of FDR/SDR with UTC, male sex, age, and MSH2 mutations are each independently associated with PHx of UTC among LS pts. LS pts with these clinical features should be considered for UTC screening/prevention strategies.