2nd Line Therapy Research Articles

Deviation from Guidelines in Use of Eltrombopag and Romiplostim in Clinical Practice for Children with Primary Immune Thrombocytopenia; Multi-Center Egyptian Experience

Background: Primary immune thrombocytopenia (ITP) has been treated with steroids or immune-suppressive. Thrombopoietin receptor agonists (TPO-RAs), changed the treatment landscape for ITP. Romiplostim and Eltrombopag were FDA approved for use in pediatric patients ≥1 year with ITP of >6 months' duration and insufficient response to previous therapy. Following the guidelines is not always feasible in practice. Aim and Methodology Centers treating more than 25 new cases/year with good recording system were included; aiming to report outcome, adverse events (AEs) and deviation from guidelines. Newly diagnosed ITP children were excluded. Data was collected from January 2017- June 2019; children age >1 to 18 years with persistent ITP (3-<12 months) or chronic (≥12 months), who had previously been treated with ≥1 previous ITP therapy, and had platelet counts (PC) persistently <30×109/l with moderate-severe bleeding. Eltrombopag was described in a dose of 25 mg/day for those > 1 to 12 years; or in 50 mg/day for those >12-18 years; dose was escalated to 50 or 75mg/day for those 6-12 and >12 years respectively on failure to have PC > 50 x 109/L. Weekly CBC and self-record of bleeding for 1st 24 week then bi-weekly. Failure to show a good response; Eltrombopag dosing should be adjusted to achieve that goal and not to exceed 200 × 109/L. Romiplostim was used in 1 ug/kg and escalated up to 10 ug/kg according to response. Serious AEs were reported to ethical committee within 24 hours. Results Two years Observational study of 204 out of 1080 primary ITP (268 persistent and 812 chronic); 55% females median age 8 years, received Eltrombopag (n=186), Romiplostim (n= 18) from 3-30 months was prescribed after failure of 1-5 lines of therapy in 15% of Persistent ITP and 20% of chronic ITP. Adequate response at 24 weeks in 60% on Eltrombopag or Romiplostim had a significant reduction in both skin-related and non-skin-related bleeding symptoms). However 50% discontinued treatment; (40% due to inadequate response, 8% irregular availability and 2% due to SAEs). Deviation from guidelines in 40%; (15% started Eltrombopag early between 3-6 months who showed a higher response rate; half of them could stop it without drop of PC); while 20% continued Eltrombopag for >12 month with lack of response after dose escalation at 24th week and 5% were not following the described dose or the regular monitoring. 40% of chronic ITP patients achieved platelet counts of >50 x 109/L or more at least twice. Common adverse events included; headache (10%). myalgia (10%), rhinitis (8%), diarrhea 8% Serious adverse events occurred in 4 (1 elevated transaminases, one unrelated life-threatening bleeding and two high PC; >1000 x109/L). Conclusion: TPO-RAs were used in almost 15% of persistent and 20% of chronic ITP as 2nd line or more therapy and in 90% was Eltrombopag; which produced an excellent response for those 3-6 months; deviating from guidelines. It showed a sustained platelet response in 40% of patients with chronic ITP, however it should be stopped if showing poor response after dose escalation. Disclosures No relevant conflicts of interest to declare.

Real World Population-Based Exploration of the Pathology Subtyping and Treatment-Modalities of Diffuse Large B-Cell Lymphoma in Belgium in Relation to Survival

Objective We report on the real world population-based study of patterns of care of DLBCL in Belgium (2013-2015) with a specific focus on the elderly population. Methods The Belgian Cancer Registry (BCR) collects, processes and analyses data on all new cancers diagnosed in Belgian residents by independent collection of double input: oncological care programs and pathology reports. Coded data were thus obtained of all adult (≥ 20 year) DLBCL diagnosed between 2013 and 2015 (n=1,890). From pathology reports we extracted immunohistochemistry (IHC) expression of CD10, BCL2, BCL6, IRF4 and MYC proteins, cell of origin (COO) classification estimated by Hans algorithm and BCL2, BCL6 or MYC gene translocation by FISH and/or PCR. Belgian health insurance data were used to infer DLBCL treatment modalities (chemotherapy schemes based on the combination of reimbursed drugs, HSCT and/or radiotherapy received) as well as to assess comorbidities. First-line treatments were grouped into 3 main categories: "standard" R-CHOP (≥6 or ≥4 cycles if Ann-Arbor = 1, including R-miniCHOP); other anthracycline containing schemes (other R-CHOP, CHOP, (R-)ACVBP, (R-)CHOP-like, intensified regimens); non-anthracycline treatments (COP and bendamustine schemes, palliative treatments). Results COO was available in 63% of cases; KI-67, BCL2, BCL2 & MYC expressions in 58%, 62% and 16% of cases respectively; MYC, BCL2 & MYC gene rearrangements in 11% and 9% of cases. Of the evaluable cases, 49% were double expressor (DE) and 10% were double-hit DLBCL (FISH only performed in ±10%). The negative prognostic markers identified from univariable models were: age, WHO PS, Ann-Arbor stage, non-GCB COO, MYC rearrangement, BCL2 expression, BCL2/MYC DE, comorbidities, other malignancies. First line systemic treatment was started in 84% of patients (Rituximab-containing in 96%) divided in standard R-CHOP (52%), other anthracycline schemes (39%) and non-anthracycline regimens (10%). The median [IQR] delay from diagnosis to treatment was 19 [9-31] days. In 18% of treated patients 2nd line therapy was initiated for refractory (10%) or relapsed disease (8%). This contained either a platinum-derivative (with or without cytarabine), HD cytarabine, anthracycline or bendamustine in 54%, 6%, 6 and 3% of cases respectively. Autologous HSCT was performed in 67 patients (BEAM-like conditioning in 88%), allogeneic HSCT in only 4 cases (< 65 yr-old). Importantly 56% of patients were ≥ 70 yr-old (transplant-ineligible) and 44% ≥ 80 yr-old (unfit for intensive treatments). In patients older than 80 (and +85) years, no systemic treatment was administered in 38% (57%) of which 27% did receive radiotherapy. First line treatment was started in 62% (43%): "standard" R-(mini)CHOP in 22% (11%); other anthracycline schemes in 23% (13%) and non-anthracycline regimens in 17% (19%) (Table 1). In this elderly population treated with R-CHOP, the median number of cycles and interval still remained 6 and 21 days showing feasibility of dose-dense therapy. Second line therapy was started in 6% and no HSCT was performed. The 2-yr overall survival [95% IC] between the different age categories [20-59], [60-69], [70-79], [80-84] and ≥85 yr-old were 84 [80-87], 74 [69-78], 62 [58-66], 44 [38-49] and 31 [25-36], respectively (Figure 1). Survival curves of treatments by age categories showed that the older patients [70-84 yr-old] still benefit from the R-(mini)CHOP treatment (Figure 2). In the multivariable analyses the following variables were associated with a significant hazard ratio: sex, age, WHO PS, respiratory comorbidity, tumor history > 1,5 year after diagnosis, "standard" R-CHOP treatment. Conclusions This real world population-based study allows to assess patients usually excluded from clinical trials (elderly population, patients with comorbidities including malignancies (13%). Although limitations due to treatment inference and to the absence of some prognostic markers, this real world analysis of diagnostic-work up and inference of treatment modalities of DLBCL in Belgium showed that the disease characteristics of the elderly population did not seem to be different from the younger population. The majority (63%) of older patients [70-84 yr-old] are started on first line treatments with curative intent. Our study suggests that a substantial fraction of this elderly population qualifies for standard R-(mini)CHOP treatment and benefits from it. Disclosures No relevant conflicts of interest to declare.

Age and Time to Progression Predict Overall Survival (OS) in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Who Progress Following Frontline Immunochemotherapy (IC)

Age and Time to Progression Predict Overall Survival (OS) in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Who Progress Following Frontline Immunochemotherapy (IC)

Facilitating Resolution of Life-Threatening Acute Graft-vs-Host Disease with Human Chorionic Gonadotropin and Epidermal Growth Factor

Background: Acute graft-versus-host disease (aGVHD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation that fails to improve with intense immunosuppression in some patients. We hypothesized that urinary-derived human chorionic gonadotropin [uhCG] could help facilitate resolution of life-threatening aGVHD when added as supportive care via two potential mechanisms: immunomodulation (akin to its role in pregnancy) and supplementation of epidermal growth factor (EGF, to aid in epithelial repair). Methods: In phase I, 26 participants received subcutaneous injections of uhCG in addition to standard immunosuppression (13 initial therapy for Minnesota high risk aGVHD and 13 receiving 2nd line therapy). Participants underwent serial blood testing for biomarkers of hormone response, immune modulation, and aGVHD activity on study. Findings: UhCG was well tolerated, with no dose-limiting toxicities. Sixty-two percent of patients in the high-risk cohort and 54% of patients in the 2nd line cohort had a complete response at study day 28. Plasma EGF was elevated 6-fold (from 4 to 24 pg/ml, p=0.02) at 6 hours post-dose in the high risk cohort, in contrast to no peak in plasma EGF in the more severe 2nd line cohort. After 1 week of uhCG, patients demonstrated a 2-fold increase in regulatory T cell to conventional T cell ratio, suggesting immune modulation despite high dose steroids. Responding patients showed significantly lower plasma amphiregulin and higher plasma butyrate at study completion, suggesting improvement in mucosal damage over time. Interpretation: hCG is a novel, safe supportive therapy, proceeding to phase II testing at 2,000 units/m2 in high-risk aGVHD. Trial Registration: This study is registered at ClinicalTrials.gov (NCT02525029). Funding Statement: This study was funded by the BMT Fund for the Future (SGH), a Regenerative Medicine Minnesota clinical trial award (SGH), and R01 HL11879, R01 HL56067 and R37 AI34495 (BRB). SGH is a University of Minnesota Women’s Early Research Career (WERC) award recipient and conducted this study during her time as a WERC scholar. Declaration of Interests: The authors have no relevant financial conflicts of interest to disclose. SGH has provided consulting services for Incyte, Bristol Myers Squibb, Janssen, and CSL Behring. BRB receives remuneration as an advisor to Kadmon Pharmaceuticals, Inc, Five Prime Therapeutics Inc, Regeneron Pharmaceuticals, Magenta Therapeutics, BlueRock Therapeuetics and consulting services for Bristol-Myers-Squibb, Incyte, Equillium, Regimmune, Dr. Reddy, GT Biopharma and Incyte Corp; research support from Fate Therapeutics, RXi Pharmaceuticals, Alpine Immune Sciences, Inc, Abbvie Inc., Leukemia and Lymphoma Society, Childrens' Cancer Research Fund, and KidsFirst Fund, and is a co-founder of Tmunity. Ethics Approval Statement: This study was approved by the University of Minnesota Institutional Review Board, and all participants signed written, informed consent.

497P - Real-word efficacy of osimertinib in patients with metastatic EGFRm NSCLC: An interim analysis from a multi-center study in China

BackgroundThe EGFRm rate in metastatic NSCLC is 30%∼40% in China. Osimertinib, 3rd generation EGFR-TKI, is approved as the 1st line treatment for patients with advanced EGFRm NSCLC and 2nd line treatment for patients with EGFR T790M positive advanced NSCLC globally, and only is approved as the 2nd line treatment in China by now. This study is to investigate the efficacy of Osimertinib in patients with metastatic EGFRm NSCLC in the real word clinical setting in China. MethodsThis multi-center study was conducted in 13 medical centers in China from April 2017 to May 2019 (Clinical trial ID: 1800019903). Patients with metastatic EGFRm NSCLC received by Osimertinib were enrolled into this study. All data were collected and analyzed on China Multi-center Lung Cancer Precision Medicine Registry RWE Box. ResultsA total of 346 patients with metastatic EGFRm NSCLC were enrolled in this study (female: 56.5%, male: 43.5%). 95.1% patients were adenocarcinoma, 2.3% patients were squamous carcinoma and 1.7% patients were adenosquamous carcinoma. The percentage of Osimertinib as 1st line, 2nd line, 3rd line, and more than 3rd line therapy was 10.4%, 55.8%, 21.4% and 12.6%, respectively. 42.5% patients were identified as the secondary T790M (+)after failure of the 1st line EGFR-TKI. For patients (N = 145) with T790M (+) metastatic NSCLC treated by Osimertinib as 2nd line therapy, the ORR was 75.1%, the mPFS was 276 days. Subgroup analysis showed that for those with both T790M (+) and CNS metastasis (N = 146), the mPFS was 280 days and CNS ORR was 67.2%. Interestingly, the CNS ORR was 34.4% for those with T790M (-) of CNS metastasis. In patients (N = 193) who had progressed after 2nd line Osimertinib, 78.9% received chemotherapy, 13.4% received bevacizumab combined with chemotherapy, and 7.7% received immunotherapy, respectively. ConclusionsOsimertinib was generally used as 2nd line treatment in patients who were resistance to the 1st line EGFR-TKI in China. Real-word data further demonstrated and validated the similar efficacy of Osimertinib as 2nd line therapy in China as that previously reported clinical trials. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

490P - Outcomes of sequential epidermal growth factor receptor tyrosine (EGFR) tyrosine kinase inhibitor (TKI) therapy in patients with advanced non-small cell lung carcinoma (NSCLC)- a real-world institutional experience

BackgroundEGFR T790M mutations have been reported to occur in about 50% of patients (pts) at progression on 1st/2nd generation EGFR TKI therapy. These pts benefit from treatment with 3rd generation EGFR TKI osimertinib. However, observational real-world studies show that the proportion of pts receiving 2nd line osimertinib is lower than expected. We aimed to evaluate these treatment patterns and outcomes in our institution. MethodsIn this prospective observational study, survival, response and treatment data was collected from pts with EGFR mutant advanced NSCLC who received EGFR TKIs in the 1st line, who were treated in our institution from September 2012 to December 2017. Institutional approval was obtained and all patients provided written, informed consent. Results108 pts (median age 65 years, 54% females, 75% never smokers, 54% EGFR exon 19 deletion) were enrolled of whom 48 (44%) received gefitinib, 38 (35%) erlotinib and 22 (20%) afatinib in the 1st line. The median overall survival (OS) was 33.1 months (95% CI 24.5-41.7) and median progression free survival (PFS) was 11.1 months (95% CI 8.5-13.7). 83 pts (77%) had progressed at the time of analysis, and 48/83 patients (58%) underwent T790M testing. Of these, 25/48 (52%) were T790M positive. 21/83 pts went on to receive osimertinib in the 2nd line (25% of all patients who progressed on 1st line therapy)- OS was not reached in these pts. 12/83 pts received 2nd line chemotherapy (15%); 32/83 pts (39%) did not receive any 2nd line treatment. OS was 42.3 months (95% CI 24.2-50.4) and 18.2 months (95% CI 11.6-24.7) in these groups respectively. ConclusionsIn this prospective real-world study, a significant proportion of patients did not receive 2nd line therapy after progression on 1st/2nd generation TKIs. The rates of T790M mutations when tested was comparable to that reported in the literature. Some reasons for not receiving 2nd line therapy included low testing rates for EGFR T790M and patient fitness for 2nd line therapy. This suboptimal use of osimertinib in the 2nd line setting, together with favourable PFS data for osimertinib in the 1st line, favours the upfront use of osimertinib. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureC.S. Tan: Honoraria (self): AstraZeneca; Honoraria (self): Merck; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Novartis; Honoraria (self): Eli-Lilly; Honoraria (self): Eisai; Honoraria (self): BMS. R.A. Soo: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): Celgene; Honoraria (self): Ignyta; Honoraria (self): Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Taiho; Honoraria (self): Takeda; Honoraria (self): Yuhan. All other authors have declared no conflicts of interest.

The National Registry of treatment regimens in patients with metastatic castration-resistant prostate cancer in the Russian Federation

Background. In Russia in 2018, prostate cancer in 40.4 % of patients was detected in stages III–IV, which requires combined and complex treatment, including hormone therapy. In the course of treatment, the tumor inevitably acquires the features of castration resistance. Currently, there are several drugs for the treatment of metastatic castration-resistant prostate cancer (mCRPC), however, there are still no standards for the optimal drug choice in patients with mCRPC, data on adverse events, duration and quality of life of patients.The study objective is describe treatment regimens for patients with mCRPC who are receiving chemotherapy/hormone therapy as the 1st and 2nd line of therapy, describe the characteristics of patients and diseases, justify the choice of therapy, describe the response of a tumor to the treatment, the types of disease progression during chemotherapy and hormone therapy, reasons for the discontinuation of treatment, treatment sequence, assessment of the overall and progression-free survival.Materials and methods. The study included and analyzed 341 patients from 41 medical institutions in Russia. The total follow-up for each patient was up to 24 months, except of the cases of death of a patient or withdrawal from the observation.Results. At the time of the initial diagnosis of prostate cancer in 198 patients (58.1 %) stage IV cancer was detected. The Gleason index of 8–10 points was determined in 118 (40.5 %) patients. The median prostatic specific antigen level (min–max) was 42.1 ng/ml (0.075– 11 743 ng/ml). Medical castration was underwent in 304 (89.1 %) patients. Duration of androgen deprivation therapy <6 months – 26 (7.6 %) patients, ≥6 months <24 months – 138 (40.5 %), ≥24 months – 142 (41.6 %), not performed – 33 (9.7 %). Localization of metastases to regional lymph nodes was detected in 101 (29.8 %) patients, bones – 293 (86.4 %), liver – 12 (3.5 %), lung – 24 (7.1 %), brain – 3 (0.9 %), other localizations – 29 (8.6 %). At the end of the observation period, 158/341 (46 %) of the patients were alive, 97/341 (28.4 %) patients died and 73/341 (21.4 %) of the patients were lost for follow-up. The results of treatment using 1st line therapy were evaluated in 317 patients. The treatment was interrupted in 163/317 (51.4 %) cases. The main reason for the cessation of treatment (131/163, 80.3 %) was the progression of the disease. The 2nd line therapy was started in 124 patients. Treatment using the 2nd line therapy was discontinued in 62 patients (50.8 %). The reason for the cessation of the treatment in 41 patients (68.3 %) was the progression of the disease, in 11 patients (17.7 %) – the decision of the patient, in 1 patient (1.6 %) – non-hematological toxicity, in 11 patients (17.7 %) – other reasons.Conclusion. This study shows the epidemiological patterns of mCRPC, the approaches to treating the disease and the results in real clinical practice during the diagnosis and treatment of mCRPC in the Russian Federation. In the Russian patient’s population, the detection of prostate cancer remains at a high level in stage IV in which a patient has distant metastases (58.1 % of patients), while the high frequency of prostate cancer metastasis in bones is confirmed (86.4 % of patients). Long-term drug treatment of mCRPC is possible in the minority of patients, of all patients who start 1st line chemotherapy, the 2nd line of therapy is started only in 36.4 % of patients.

Body mass index in non-small cell lung cancer patients treated with anti-PD-1 immune checkpoint inhibitors.

68 Background: Previous retrospective analyses have revealed higher response rates and a trend towards longer progression-free survival (PFS) and overall survival (OS) in response to immune checkpoint inhibitors (ICIs) in overweight patients. There are few reports concerning the association between the overweight state and the efficacy of ICIs specifically in non-small cell lung cancer (NSCLC) patients. We investigated the association between the body mass index (BMI) and the efficacy of ICIs in patients with NSCLC. Methods: Patients with advanced NSCLC who received ICI therapy (nivolumab or pembrolizumab) at the National Cancer Center Hospital from January 2016 to December 2018 were included in this retrospective cohort study. Based on their BMI, the patients were categorized into the overweight (A) group (BMI ≥25) and the non-overweight (B) group (BMI < 25). The PFS was compared between the two groups as the primary outcome. Results: Data of a total of 323 patients (median age, 63 years) were analyzed; 87 (26.9%)/43 (13.3%)/193 (59.8%) patients received pembrolizumab as 1st line therapy, pembrolizumab as 2nd line therapy, and nivolumab, respectively. Tumor proportion score was ≥50% in 58.4% (139/238) patients. The ECOG-PS was ≥2 in 37 patients (11.5%). The median body weight was 58.1, and the median BMI was 21.4. Of the 323 patients, 46 (14.2%) were categorized into group A (overweight) and 277 (85.8%) into group B (non-overweight). The median PFS and OS in two groups were as follows: A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25], p = 0.38), and A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43], p = 0.64), respectively. In accordance with the ICI regimen that the patients received, the PFS was A, 7.9 m/B, 7.8 m (HR 0.86, 95%CI [0.37-2.04], p = 0.74) in the patients who received pembrolizumab as 1st line therapy, A, 7.5 m/B, 5.3 m (HR 0.60, 95% CI [0.18-2.00], p = 0.40) in the patients who received pembrolizumab as 2nd line therapy, and A, 6.5 m/B, 4.4 m (HR 0.84, 95% CI [0.52-1.36], p = 0.48) in the patients who received nivolumab. Conclusions: Overweight NSCLC patients treated with ICIs showed a trend (non-statistically significant) towards a longer PFS as compared to non-overweight patients.

1533P - Treatment patterns of EGFR mt+ NSCLC IV pts: Real-world data of the NOWEL network

BackgroundThe percentage of pts switching from 1st gen TKI in 1st line to 3rd gen TKI in 2nd line seems to be low with 30% and it is questionable whether these data represent real world treatments. Therefore, we investigated the treatment pattern and especially the attrition rate between 1st and 2nd line therapy in EGFR mt+ pts from the NOWEL network. MethodsA retrospective study of 1539 pts with non-squamous NSCLC IV was accomplished. 965/1536 (63%) pts were tested for EGFR mt+ between 2009-2018. 148/965 (15%) pts with an EGFR mt+ were identified. To calculate PFS and OS we used Kaplan Meier methods and the log rang test for p-values. ResultsBaseline characteristics of 148 EGFR mt+ pts: median age 65 yrs; 64% female (n=95/148); 64% never/light smoker (n=94/148). 135/148 pts (91%) carried an EGFR mt+ either del19 (n=81) or L858R (n=55). 144/148 pts were treated with TKI on 1st or 2nd line (after chemotherapy) and 4 pts received no therapy at all. 14/144 pts are still on 1st line, 9 pts were lost to follow-up and 3 pts died while on 1st line therapy. We identified 118/144 candidates for 2nd line therapy (because of progression on 1st line TKI) and only 84/118 (70%) pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd line therapy because of bad PS (n=26), pts refusal (n=2), fast progression (n=6) and death (n=2). After accessibility of 3rd gen TKI 72 pts were candidates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy. MOS of pts receiving 2nd line therapy after access to 3rd gen TKI was 35mo for pts with 2nd line therapy vs. 10mo without 2nd line (p<0.000). 32/51 pts (63%) were tested for T790M and 20/32 (62%) were T790M+. Highest T790M testrate in one center was 22/28 (79%). 16/20 (80%) T790M+ pts received 3rd gen TKI for 2nd line therapy. MOS of pts receiving 3rd gen TKI (n=31) was 51mo vs. 25mo for pts without 3rd gen TKI (p<0.002). ConclusionsIn real world, a significant number of pts treated with 1st or 2nd gen TKI do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS, death and no testing for T790M in a minority of cases. These data are important for the interpretation of the OS data of the FLAURA study as they reflect real world treatment algorithms in dedicated German lung cancer centers. Legal entity responsible for the studyCarl v. Ossietzky University of Oldenburg, Prof. Dr. Griesinger. FundingHas not received any funding. DisclosureJ. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Falk: Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self): AstraZeneca. F. Griesinger: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celegene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Siemens; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.

EP1.04-13 Immunotherapy Versus Chemotherapy for Previously Treated Metastatic NSCLC. Results from Daily Clinical Practice

Immunotherapy has shown promising results in the treatment of mNSCLC. The aim of this retrospective analysis was to compare the efficacy and toxicity of chemotherapy and immunotherapy in the 2nd line treatment of mNSCLC. Fifty-nine patients with advanced NSCLC consecutively admitted in our Medical Oncology Department were enrolled in the study. A total of 83% were men, and 17% women. Patients had median ECOG 1 (0-3), median age 68 (47-86) years, squamous(32%) and non-squamous histology(68%). All of them were previously treated with 1st line chemotherapy regimens. Following disease progression, they received either chemotherapy or immunotherapy as 2nd line therapy. We compared both the efficacy and toxicity of the two therapeutic options. In the immunotherapy arm, patients received either Nivolumab, or Pembrolizumab. The number of patients whose disease progressed after receiving chemotherapy in the 2nd line, was similar to those who received immunotherapy. However, time to progression, was significantly shorter in the chemotherapy arm (p=0,015). There was significant difference in disease progression probability between the two arms in both 3 and 6 months (p<0,05). Patients with at least one adverse event had 2,27 times higher probability of disease progression. Median overall survival was 8 months for the chemotherapy arm in second line, compared to 14 months in the immunotherapy arm. There was no difference in survival between the two arms in the 6 month evaluation (p>0,05). However, in the 12 and 18 month evaluation, survival rates were significantly higher for patients in the immunotherapy arm (p=0,006 και p=0,001 respectively). Patients who received immunotherapy in 2nd line, had siginificantly higher overall survival rates, compared to those that received chemotherapy (p=0,006). There was no correlation between PD-L1 expression levels and clinical benefit. Immunotherapy had a better safety profile compared to chemotherapy. Data from our daily clinical practice are in line with current literature.

759P - Outcomes of hepatocellular carcinoma (HCC) patients treated with nivolumab: The Mount Sinai Hospital experience

BackgroundNivolumab (N), an IgG4 monoclonal antibody to PD-1, yields long-term disease control and prolonged survival in some patients (pts) with HCC, leading to its approval by the FDA in 2017 as 2nd line therapy after sorafenib. We present our institutional experience with N in the treatment of HCC at Mount Sinai Hospital. MethodsMedical records of HCC pts treated with N until progression or intolerable toxicity between June 2016 and July 2018, were reviewed. Response was evaluated by RECIST 1.1. Overall and Progression free survival (OS, PFS) were estimated by Kaplan-Meier method. Results104 pts (84% male, median age 66 [29-89] years) were identified. 24 (23%) pts were Asian, 26(25%) Black, 30(29%) White and 24(23%) unknown. Hep C was the most common risk factor in 50 (48%) pts, followed by Hep B in 34(32%) with co-infection in 7 (6%) pts, NASH in 10 (9%), Alcohol in 8(7%) and other including HIV in 10 (9%)pts. Cirrhosis was present in 83 (80%) pts. Child Pugh score (N=96) and was A in 64 (67%) and B in 32 (33%) pts. Barcelona Clinic Liver Cancer (BCLC) stage was B in 21 (20%) and C in 83 (80%) pts. 67 (64%) pts received 1st line systemic therapy with N. Among the 37 (36%) treated with N in subsequent lines, 27 (73%) had progressed on Sorafenib. Loco-regional therapies (LRT) including Y90 and TACE were given concurrently with N in 32(31%) pts. The median duration of treatment was 26 (2-149) weeks and median follow up was 17 months (95% CI (15.7, 20.7)). Objective response rate was 20% including 10(10%) complete responders (CR), all of whom received concurrent LRT. 39(37%) pts had progressive disease (PD) and 40(38%) had stable disease (SD). Median duration of response was 9 (1-31) months. Median OS and PFS are shown in the table.Table759PTableOS (months)PPFS(months)PBy line:First230.1013160.1394Subsequent126By response:CR/PRNot Reached<0.0001SD23PD7 ConclusionsHCC pts treated at our institution frequently received N in first line and 31% received concurrent LRT. Survival did not differ statistically between first vs subsequent line N. Our real-world experience with N in HCC appears comparable to data from the checkmate-040 study. Legal entity responsible for the studyMount Sinai Hospital. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

1189PD - Determinants of response of HER2+ gastric cancer (GC) vs gastroesophageal junction adenocarcinoma (GEJ) to margetuximab (M) plus pembrolizumab (P) post trastuzumab (T)

1189PD - Determinants of response of HER2+ gastric cancer (GC) vs gastroesophageal junction adenocarcinoma (GEJ) to margetuximab (M) plus pembrolizumab (P) post trastuzumab (T)

829TiP - Multicenter randomized phase II trial of 5-fluorouracil/leucovorin (5-FU/LV) with or without liposomal irinotecan (nal-IRI) in metastatic biliary tract cancer (BTC) as second-line therapy after progression on gemcitabine plus cisplatin (GemCis): NIFTY trial

BackgroundPatients with BTC have dismal prognosis with 5-year survival of less than 10%. GemCis is the globally established first-line therapy based on the phase III ABC-02 trial. However, there is no standard second-line therapy after failure of 1st line GemCis, although 5-FU-based therapy has been widely used. Nal-IRI (Onivyde®) comprises irinotecan sucrosofate salt encapsulated in pegylated liposomes that protect the drug from premature conversion in the liver. This randomized phase 2 trial is designed to compare the clinical outcomes between nal-IRI plus 5-FU/LV with 5-FU/LV alone as 2nd line therapy in patients with BTC who progressed on 1st line Gem/Cis. Trial designNIFTY trial is a multicenter, open-label, randomized, phase II trial and 5 referral cancer centers in Korea participated in this study. Histologically documented biliary tract cancer (intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer), documented progression on 1st line Gem/Cis, and at least one measurable lesion are key inclusion criteria. Eligible patients are randomized with 1:1 ratio to experimental arm (80mg/m2 irinotecan hydrochloride trihydrate salt equivalent to 70mg/m2 irinotecan free base over 90minutes, followed by 400mg/m2 LV over 30min, and then 2400mg/m2 5-FU over 46h, every 2 weeks) and control arm (400mg/m2 LV over 30min, and then 2400mg/m2 5-FU over 46h, every 2 week). Response evaluation is graded by RECIST v1.1 and conducted every 6 weeks. Primary endpoint is progression-free survival and secondary endpoints are overall survival, response rates, quality of life assessed by EORTC QLQ-C30 and safety profile. We hypothesized that the addition of nal-IRI to 5-FU/LV would enhance the PFS to median 3.3 months (P1) from median 2.0 (P0) with 5-FU/LV alone. With alpha of 0.05, power of 80%, and drop-out rates of 10%, a total of 174 patients (87 patients per each arm) are needed based on this hypothesis. As of March 2019, a total of 89 patients (51% of the target number) are enrolled. Clinical trial identificationNCT03524508. Legal entity responsible for the studyThe authors. FundingShire and Servier. DisclosureC. Yoo: Research grant / Funding (self): Shire; Advisory / Consultancy, Research grant / Funding (self): Servier; Honoraria (self): Ipsen. All other authors have declared no conflicts of interest.

The comparison of Carfilzomib, and dexamethasone versus pomalidomide-based combination chemotherapy after a 2nd-line therapy in relapsed and refractory multiple myeloma patients

New class of drugs are emerging in heavily pretreated patients in clinical trials, carfilzomib, and dexamethasone (Kd) and pomalidomide and dexamethasone with or without cyclophosphamide (Pd or PCd) are still important options for treatment of relapsed and/or refractory multiple myeloma (RRMM). However, direct comparison of the efficacy of carfilzomib and pomalidomide has not been evaluated. The aim of this study was to compare the efficacy and safety profile of Kd and pom-based regimens in RRMM patients after 2nd line chemotherapy in the real world clinical setting. Patient and method: Two-hundred and twenty-five patients from 14 hospitals participating in the Korean multiple myeloma working party (KMMWP) were retrospectively analyzed by review of medical records. Multiple myeloma patients who relapsed or were refractory to 2 or more lines of chemotherapy regimens and who had been treated with Kd (Kd group, N=44) or pomalidomide-based chemotherapy (Pom group, N=181) were included. When patients who had been administered with both carfilzomib and pomalidomide-combination chemotherapies sequentially, the drug used in advance was analyzed. The pomalidomide group included patients who had undergone Pd (N=108) and PCd (N=73).

926P - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison

BackgroundErda, a pan-fibroblast growth factor receptor (FGFR) inhibitor recently received accelerated US FDA approval for locally advanced or metastatic urothelial cancer (mUC) in adult patients (pts) with FGFR2/3 alterations who progressed on≥1 prior platinum-containing chemotherapy, based on a single-arm phase 2 study. In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) was used to compare the efficacy of erda relative to available therapies in mUC pts. MethodsSystematic literature review was performed to identify published randomized controlled trials (RCTs) of 2nd-line treatments (from 1990-on) in mUC pts with unknown FGFR status. Individual patient-level data (IPD) were used from the phase 2 study (NCT02365597) in mUC pts treated with erda (8mg/day). ORR (primary endpoint), overall survival (OS) and progression-free survival (PFS) were compared using an unanchored MAIC. The IPD were weighted to match the aggregated data from comparator studies. ResultsNine relevant RCTs of 6 comparators (docetaxel [D], vinflunine [V], pembrolizumab [Pb], atezolizumab [A], paclitaxel [P], and mixed-chemotherapy [D, V or P]) that were identified could be matched with. The matching-adjusted odds ratios (OR) for ORR were consistently >1 vs all comparators, suggesting higher ORR with erda treatment over all comparator 2nd-line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were <1, suggesting better outcomes (PFS/OS) with erda. Results from the sensitivity analyses showed varied statistical significance, however, the overall trends were relatively similar. Study limitations: availability of comparable endpoints and baseline characteristics; small sample size of the erda study.Table926P MAIC results for base case scenario: Erda (in FGFR+ pts) vs available 2nd-line therapies in pts with unknown FGFR statusTableComparatorStudyN (Neff)ORR (OR [95% CI])OS (HR [95% CI])PFS (HR [95% CI])PembrolizumabNCT0225643679 (40)2.26 [1.11; 4.59]*0.61 [0.37; 0.99]*0.77 [0.58; 1.03]AtezolizumabNCT0230280774 (45)6.80 [3.55; 13.02]***0.58 [0.37; 0.92]*Mixed-chemotherapyNCT0225643679 (45)4.15 [2.04; 8.46]***0.54 [0.35; 0.85]**0.77 [0.56; 1.07]Mixed-chemotherapyNCT0230280774 (51)6.26 [3.37; 11.63]***0.54 [0.34; 0.84]**DocetaxelaNCT0128246368 (45)3.71 [1.11; 12.35]*0.72 [0.41; 1.25]0.51 [0.32; 0.80]*DocetaxelNCT0088033478 (42)3.98 [1.48; 10.74]**0.52 [0.31; 0.87]*0.84 [0.56; 1.26]DocetaxelNCT0178054584 (47)6.02 [2.48; 14.63]***0.37 [0.23; 0.61]***DocetaxelNCT0242612578 (63)3.46 [1.80; 6.66]**0.63 [0.47; 0.84]*VinflunineaNCT0031523778 (53)4.74 [2.21; 10.18]***0.57 [0.39; 0.84]**VinflunineNCT0183023161 (32)1.51 [0.45; 5.10]0.49 [0.24; 0.99]*0.96 [0.51; 1.81]PaclitaxelaNCT0094945568 (44)2.63 [1.03; 6.73]*0.59 [0.37; 0.95]*0.95 [0.64; 1.41]For most comparators, only the main characteristics (according to clinical experts; number of risk factors, ECOG, liver metastases, hemoglobin<10g/dl, visceral disease, liver/bone metastasis, metastatic disease, primary tumor site, smoking status, and time since prior therapy) were included in the base case matching process to maintain a reasonable effective sample size (Neff). aAll available characteristics were included. When type of ORR (assessment by independent review committees [IRR] or assessment by investigators) is not specified for the comparator study, IRR was used for erda as this leads to conservative results.*p≤0.05;**p≤0.01;***p≤0.0001 ConclusionsTreatment of FGFR+ mUC pts with erda may be associated with improved overall response, PFS and OS as compared to available therapies in pts with unknown FGFR status. Clinical trial identificationNCT02365597. Editorial acknowledgementPriya Ganpathy, MPharm, ISMPP CMPP™ (SIRO Clinpharm Pvt. Ltd, India) provided writing assistance and Harry Ma, PhD (Janssen Global Services) provided additional editorial support. Legal entity responsible for the studyJanssen Research & Development, LLC. FundingJanssen Research & Development, LLC. DisclosureY. Loriot: Honoraria (self), Consultancy / Advisory Role- Astellas Pharma, AstraZeneca, Janssen, Merck Sharp & Dohme, Pfizer, Roche, Ipsen, Seattle Genetics, Sanofi; Research Funding- Sanofi (Inst) S. Van Sanden: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. J. Diels: Shareholder / Stockholder / Stock options, Employee and Share holder: Janssen Reserach & Development. N. Rahhali: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. D. Seshagiri: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Reserach & Development. B. Kowalski: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. S. Fleming: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. A.O. Siefker-Radtke: Consulting / Advisory Role: AstraZeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Genentech, Inovio Pharmaceuticals, Janssen, Lilly, Merck, NCCN; Speakers’ Bureau: Genentech; Research funding: Bristol-Myers Squibb, Janssen, Michael, Sherry Sutton; Fund for Urothelial Cancer: NIH, Takeda; Patents / Royalties / Other Intellectual Property: Methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.

Precision Oncology for Pancreatic Cancer across the United States: the Know Your Tumor ® experience

Abstract The Know Your Tumor initiative identifies pancreatic cancer patients across the USA eligible for molecular testing through the Pancreatic Cancer Action Network call center. Perthera, Inc obtains patient consent, coordinates molecular testing, convenes a virtual molecular tumor board, prepares a report with a ranked list of therapy options, and collects outcomes. More than 1800 patients have been enrolled from 49 states and more than 1100 reports have been delivered. DNA testing was primarily with the Foundation Medicine panel of 324 genes and includes microsatellite instability (MSI). Therapy options include clinical trials, off-label treatments, or standard-of-care chemotherapy. Approximately one quarter (26%) of patients were identified with highly actionable (HA) alterations defined as molecular alterations for which a targeted therapy is indicated based on data in any cancer type. HA alterations include mutations in BRCA1/2, ATM, PALB2 and other DNA damage-repair genes indicating treatment with a PARP inhibitor, MSI-High with a PD-1 inhibitor, and alterations in RET, NTRK, BRAF, ALK, ROS, CDK4/6, FGF, and ROS with specific targeted agents. Patients treated in the advanced setting with HA alterations who received a molecularly-matched therapy (n = 46) had a significant 1-year improvement in overall survival compared to those with HA alterations who had no molecularly-matched therapies (HR = 0.42, p=.0004, n = 143) or those with no HA alterations (HR = 0.34, p=.000002, n = 488). Progression-free survival for those receiving a molecular matched therapy as 2nd line or greater therapy (10.93 mos, n = 38) was 2.4-fold greater than those with HA alterations and their best unmatched therapy (4.53 mos, p = 0.01, n = 84) and 2-fold greater than those without HA alterations (5.37 mos, p = 0.01, n = 288). These results provide evidence in a real-world setting that support the recent change in NCCN guidelines recommending tumor profiling for patients with advanced pancreatic cancer.

834TiP - A randomized controlled, open label, adaptive phase III Trial to evaluate safety and efficacy of endoTAG-1 plus gemcitabine versus gemcitabine alone in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas failed on FOLFIRINOX treatment

BackgroundPancreatic cancer (PC) is the 4th deadliest cancer in Europe, with more than 95% of those affected dying from the disease and is set to be the second greatest cause of death from cancer by 2020.(ECPC, European Cancer Patient Coalition) FOLFIRINOX regimen is the standard 1st-line treatment for PC patients with good performance status; however, there is still no standard of care in 2nd-line therapy for patients failed FOLFIRINOX. EndoTAG-1 is a novel formulation of cationic liposomes embedded with Paclitaxel, which specifically displays antivascular and antiangiogenic activity. By binding and internalizing at tumor endothelial cells after intravenous administration, the cytostatic and cytotoxic activities of paclitaxel are targeted to the activated tumor endothelial cells. Trial design•Patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas failed on FOLFIRINOX treatment will be screened and randomized into one of the two arms in the study (n=218). •ArmA: EndoTAG-1 and Gemcitabine Patients will be administrated with EndoTAG-1 (22mg/m²) twice weekly plus gemcitabine (1000mg/m²) once weekly for 1 cycle (8 weeks), which consisting of 3 weeks of treatment and 1 week rest, followed by 3 weeks of treatment and 1 week rest. The treatment will be kept until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent. •ArmB: Gemcitabine Patients will be administrated with Gemcitabine (1000mg/m²) once weekly for 1 cycle (8 weeks), which consisting of 3 weeks of treatment and 1 week rest, followed by 3 weeks of treatment and 1 week rest. The treatment will be kept until any one of the following occurs: progressive disease or unacceptable toxicity or withdrawal of consent. Clinical trial identificationNCT03126435, other study ID numbers:CT4006. Legal entity responsible for the studySynCore Biotechnology Co., Ltd. FundingSynCore Biotechnology Co., Ltd. DisclosureAll authors have declared no conflicts of interest.

Drug resistance and optimizing dolutegravir regimens for adolescents and young adults failing antiretroviral therapy

The integrase strand inhibitor dolutegravir (DTG) combined with tenofovir and lamivudine (TLD) is a single tablet regimen recommended for 1st, 2nd and 3rd-line public health antiretroviral therapy (ART). We determined drug resistance mutations (DRMs) and evaluated the predictive efficacy of a TLD containing regimen for viremic adolescents and young adults in Harare, Zimbabwe. We sequenced plasma viral RNA from HIV-1-infected adolescents and young adults on 1st and 2nd-line ART with confirmed virologic failure (viral load >1000 copies/ml) and calculated total genotypic susceptibility scores to current 2nd, 3rd line and DTG regimens. A total of 160 participants were genotyped; 112 (70%) on 1st line and 48 (30%) on 2nd line, median (interquartile range) age 18 (15-19) and duration of ART (interquartile range) was 6 (4-8) years. Major DRMs were present in 94 and 67% of 1st and 2nd-line failures, respectively (P < 0.001). Dual class resistance to nucleotide reverse transcriptase inhibitors and nonnucleotide reverse transcriptase inhibitors was detected in 96 (60%) of 1st-line failures; protease inhibitor DRMs were detected in a minority (10%) of 2nd-line failures. A total genotypic susceptibility score of 2 or less may risk protease inhibitor or DTG monotherapy in 11 and 42% of 1st-line failures switching to 2nd-line protease inhibitor and TLD respectively. Among adolescents and young adults, current protease inhibitor-based 2nd-line therapies are poorly tolerated, more expensive and adherence is poor. In 1st-line failure, implementation of TLD for many adolescents and young adults on long-term ART may require additional active drug(s). Drug resistance surveillance and susceptibility scores may inform strategies for the implementation of TLD.

SIGNIFICANCE OF ADDITIONAL CHROMOSOMAL ABNORMALITIES FOR THE OUTCOMES AFTER THE SECOND LINE NILOTINIB THERAPY IN THE CHRONIC MYELOID LEUKEMIA PATIENTS

Background. There is limited information about impact of additional chromosome aberrations (ACA) on the efficacy of the 2nd line nilotinib therapy. Objective. The aim of the study was to analyze significance of ACAs for the outcome after second line tyrosine kinase inhibitors (TKI) therapy with nilotinib in the chronic myeloid leukemia (CML) patients, who experienced previous imatinib therapy failure. Methods. The CML patients in chronic phase treated with nilotinib after imatinib failure were analyzed for outcomes. Results. Among a total of 114 patients, 18 patients (15.8%) had ACAs at the beginning of the 2nd line therapy with nilotinib. Seven patients (38.9%) of 18 had variant translocations and 11 patients (61.1%) had other chromosomal abnormalities in addition to t(9;22), known as clonal evolution. Complete cytogenetic response (CCR) at 12 months was achieved in 37.5%, 42.8% and 45.5% (p=0.842) of patients with classic t(9;22) translocation, variant translocations and ACAs respectively. In the patients with variant translocations t(9;V;22) or clonal evolution treated with nilotinib after the imatinib failure, the CCR and major molecular response (MMR), event free survival (EFS), progression free survival (PFS) and overall survival (OS) rates did not differ from those in the CML patients with t(9;22) only. At the same time quantitative characteristics of leukemic and ACA clones had prognostic value for CCR. The increased number of Ph-positive cells and the number of cells with the ACA at the start of nilotinib therapy reduced the probability of CCR. Conclusions. Higher nilotinib inhibitory activity compare with imatinib allows us to overcome imatinib resistance in the CML patients regardless of the ACA presence at the beginning of nilotinib therapy.

MORPHOLOGIC AND MOLECULAR FEATURES OF PRIMARY GLIOBLASTOMA IN PATIENTS SURVIVING MORE THAN 3 YEARS

Primary glioblastoma (GB) is a rapidly progressing central nervous system tumor with aggressive biological behavior. Long-term glioblastoma survival, defined as survival beyond 3 years, is a rare phenomenon. Various factors contributing to such prolonged lifespan have been proposed.Aim. This study aimed to compare demographic, clinical, morphologic, immunohistochemical and molecular features of primary GB in patients with different survival.Material andMethods. This prospective study included 69 patients, who were treated at A.L. Polenov Neurosurgery institute. The analysis considered clinical, morphologic, immunohistochemical (Ki67, P53, INA , EGFR) and genetic (MGMT, VEGF and PDGFRA gene expression; ID H1/2 mutational status, 1p/19q co-deletion) characteristics of the disease.Results. 11 (15.9 %) patients survived beyond 3 years. Prolonged survival was associated with younger patient age (p=0.002), use of more than 6 cycles of temozolomide in the 1st line therapy (p=0.016), use of the 2nd line therapy (p=0.017) and low level of MGMT expression in the tumor tissue (p=0.038). Other factors including patients’ gender, VEGF and PDGFRA mRNA expression levels, ID H1 mutation, 1p/19q deletion, and the immunohistochemical markers Ki67, p53, INA , EGFR, were not associated with prolonged survival (p&gt;0.05).Conclusion. Prolonged survival in GB patients is a non-random event and can be explained by several clinical and biological factors. A high percentage of 3-year survival of GB patients in our study may be explained by an individual approach to treatment and intensive chemotherapeutic tactics (from 6 to 15 cycles of temozolomide in the 1st line therapy and use of the 2nd line therapy), as opposed to standard short treatment protocols.