Background: Prolgolimab is an IgG1 anti-PD-1 monoclonal antibody with the Fc-silencing 'LALA' mutation. The phase III DOMAJOR study assessed efficacy and safety of prolgolimab in combination with pemetrexed and platinum-based chemotherapy vs placebo in combination with pemetrexed and platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC). Methods: 292 patients with advanced non-squamous NSCLC were randomized 1:1 to receive 4 cycles of pemetrexed, platinum-based drug and either prolgolimab (3 mg/kg Q3W) or placebo followed by prolgolimab/placebo with pemetrexed until disease progression or toxicity (<= 36 months). The primary endpoint was overall survival (OS). Results: After a median follow-up of 18 months, the median OS was not reached (95 % CI, 22.28 - NA) in the prolgolimab-combination group vs 14.6 months (95 % CI, 11.73 - 19.15) in the placebo-combination group (HR, 0.51; 95 % CI, 0.35 - 0.73, p = 0.0001). The OS improvement was independent of PD-L1 status. Median progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was 7.7 months in the prolgolimab-combination group and 5.5 months in the placebo-combination group (HR, 0.65; 95 % CI, 0.49 - 0.85, p = 0.0004). The only adverse events that were reported in at least 10 % of the patients that were significantly more frequent in the prolgolimab-combination group were blood creatinine increased and dyspnoea. Conclusion: Among patients with advanced NSCLC the addition of prolgolimab to pemetrexed and a platinum- based drug increased OS and PFS, with no new safety concerns. This benefit was retained in patients with PD- L1 negative tumors. (ClinicalTrials.gov, NCT03912389)

448 Background: T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg monotherapy is approved for patients with metastatic HER2+ GC/GEJA who have received a prior trastuzumab-based regimen. Preliminary results from DG-03 Part 2 showed feasibility and promising antitumor activity with 1L T-DXd 6.4 mg/kg (arm D) or 5.4 mg/kg (arm F) with FP and pembrolizumab in patients with esophageal adenocarcinoma/GC/GEJA. T-DXd 6.4 mg/kg and FP with pembrolizumab was associated with higher than expected toxicity; alternatively, early safety data from T-DXd 5.4 mg/kg triplet combination showed a manageable safety profile. We report updated results for arm F from DG-03 Part 2 with an approximate time-matched analysis with arm D. Methods: DG-03 (NCT04379596) is a Phase 1b/2 multicenter, open-label, dose-escalation (Part 1) and -expansion (Parts 2, 3, and 4) study. In Part 2, patients with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization–positive by local testing) esophageal adenocarcinoma/GC/GEJA, irrespective of programmed cell death ligand 1 status, and no prior treatment for metastatic disease were enrolled. In arm D, patients received T-DXd 6.4 mg/kg intravenous (IV) infusion every 3 weeks (Q3W) and FP (5-fluorouracil [5-FU] 600 mg/m 2 continuous IV or capecitabine [cape] 1000 mg/m 2 twice daily [BID]) with pembrolizumab 200 mg IV Q3W; in arm F, patients received T-DXd 5.4 mg/kg IV Q3W and FP (5-FU 600 mg/m 2 continuous IV or cape 750 mg/m 2 BID) with pembrolizumab 200 mg IV Q3W.Primary endpoint was confirmed objective response rate by investigator assessment (INV) per RECIST 1.1. Secondary endpoints included duration of response by INV and progression-free survival by INV. Safety and tolerability were also assessed. Results: A time matched analysis was performed to compare the efficacy of arm D (n=43), data cut-off (DCO) October 27, 2022, and arm F (n=32), DCO May 6, 2024, given the limited follow up of the 5.4mg/kg. The median duration of follow up for the two cohorts was 4.1 months and 4.6 months for arm D and arm F, respectively. Objective response rate for arm D was 41.9% and 59.4% for arm F. Median PFS was 6.4 months (95% CI: 5.0, NC) for arm D and 5.8 months (95% CI: 5.6, NE) for arm F. At DCO, the median overall survival in both arms was not reached. Updated time matched safety and efficacy data will be provided at the time of presentation. Conclusion: The time matched analysis shows that lowering the dose of T-DXd to 5.4 mg/kg from 6.4 mg/kg and lowering the starting dose of capecitabine, did not result in decrease in efficacy of the combination of T-DXd + FP + pembrolizumab. Funding: This study is sponsored by AstraZeneca in collaboration with Daiichi Sankyo. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). Editorial acknowledgment: Under guidance of the authors and in accordance with Good Publication Practice, medical writing and editorial support was provided by Carmen Grimaldos, PhD, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca. Clinical trial information: NCT04379596 .

Introduction. The addition of durvalumab after chemoradiation therapy in unresectable stage III non-small-cell lung cancer (NSLC) is a new standard of care.Aim. Study the features and outcomes of durvalumab maintenance treatment after chemoradiotherapy in patients with unresectable stage III NSCLC in the real-world clinical practice in Russia.Materials and methods. 50 patients with unresectable III stage NSCLC after concurrent or sequential chemoradiotherapy (CRT) were enrolled in this observational retrospective study. Median follow up time at primary analysis was 12.4 months.Results. A mean age of the patients in the study was 61.2 years (58.4-64.1; 95% CI). Most of the patients had received sequential CRT (76%, n = 38). Median time of durvalumab start from the end of CRT varied from 22 to 50 days (overall - 35 days). Estimated median PFS and OS were 10.86 months (7.78-14.01, 95% CI) and 26 months (20.19-31.81, 95% CI), respectively. There was a trend toward increased PFS in patients with smoking history: 12 months (9.79-14.2; 95% CI) versus 4,9 months (0.0-12.47; 95% CI), p = 0.2. Half of the patients without smoking history (5/10) had targetable mutations (EGFR ex 19, ALK, ROS1, cMET). Most common reported adverse events of special interest were pneumonitis grade 1-2 (36%, n = 18), leading permanent treatment discontinuation to in 6% of patients (n = 3). There were no reported cases of grade 3-4 adverse events.Conclusions. Real-world characteristic of patients in our study were different from PACIFIC trial. Sequential CRT is the most frequent treatment option in locally advanced unresectable NSCLC in Russia. Estimated PFS was shorter than in PACIFIC, but there were less cases of pneumonitis.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We present the final prespecified overall survival (OS) analysis of the open-label, phase III CLEAR study in treatment-naïve patients with advanced renal cell carcinoma (aRCC). With an additional follow-up of 23 months from the primary analysis, we report results from the lenvatinib plus pembrolizumab versus sunitinib comparison of CLEAR. Treatment-naïve patients with aRCC were randomly assigned to receive lenvatinib (20 mg orally once daily in 21-day cycles) plus pembrolizumab (200 mg intravenously once every 3 weeks) or sunitinib (50 mg orally once daily [4 weeks on/2 weeks off]). At this data cutoff date (July 31, 2022), the OS hazard ratio (HR) was 0.79 (95% CI, 0.63 to 0.99). The median OS (95% CI) was 53.7 months (95% CI, 48.7 to not estimable [NE]) with lenvatinib plus pembrolizumab versus 54.3 months (95% CI, 40.9 to NE) with sunitinib; 36-month OS rates (95% CI) were 66.4% (95% CI, 61.1 to 71.2) and 60.2% (95% CI, 54.6 to 65.2), respectively. The median progression-free survival (95% CI) was 23.9 months (95% CI, 20.8 to 27.7) with lenvatinib plus pembrolizumab and 9.2 months (95% CI, 6.0 to 11.0) with sunitinib (HR, 0.47 [95% CI, 0.38 to 0.57]). Objective response rate also favored the combination over sunitinib (71.3% v 36.7%; relative risk 1.94 [95% CI, 1.67 to 2.26]). Treatment-emergent adverse events occurred in >90% of patients who received either treatment. In conclusion, lenvatinib plus pembrolizumab achieved consistent, durable benefit with a manageable safety profile in treatment-naïve patients with aRCC.

Lung cancer is the second most common type of cancer worldwide, making up about 20% of all cancer deaths with less than 10% 5-year survival rate for the very late stage. The recent guidelines for the most common non-small-cell lung cancer (NSCLC) type recommend performing staging based on the 8th edition of TNM classification, where the mediastinal lymph node involvement plays a key role. However, most of the non-invasive methods have a very limited level of sensitivity and are relatively accurate, but invasive methods can be contradicted for some patients. Current advances in Deep Learning show great potential in solving such problems. Still, most of these works focus on the algorithmic side of the problem, not the clinical relevance. Moreover, none of them addressed individual lymph node malignancy classification problem, restricting the indirect analysis of the whole study, and limiting the interpretability of the result without giving an option for cliniciansto validate the result. This work mitigates these gaps, proposing a multi-step algorithm for each visible mediastinal lymph node segmentation and assessing the probability of its involvement in themetastatic process, using the results of histological verification on training. The developed pipelineshows 0.74 ± 0.01 average Recall with 0.53 ± 0.26 object Dice Score for the clinically relevant lymph nodes segmentation task and 0.73 ROC AUC for patient’s N-stage prediction, outperformingtraditional size-based criteria.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study did not receive any funding.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Independent Ethical Committee of the Moscow Regional Branch of the Russian Society of Radiologists gave ethical approval for this work dated 23 March 2023, protocol no. 03/2023I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.

PURPOSE Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti–programmed cell death ligand-1) plus olaparib (PARP inhibitor) in patients with metastatic UC (mUC). METHODS This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible patients with mUC. Patients (N = 154) were randomly assigned 1:1 to receive durvalumab (1,500 mg intravenously once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo. The primary end point was progression-free survival (PFS) assessed by investigators per RECIST version 1.1. Secondary end points included overall survival in all patients and PFS in patients with HRRm. RESULTS Overall, median PFS was 4.2 months (95% CI, 3.6 to 5.6) for durvalumab plus olaparib and 3.5 months (95% CI, 1.9 to 5.1) for durvalumab plus placebo (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value, .789). Median overall survival was 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3), respectively (HR, 1.07; 95% CI, 0.72 to 1.61). In the 20% of patients with HRRm, median PFS was 5.6 months (95% CI, 1.9 to 8.1) and 1.8 months (95% CI, 1.7 to 2.2), respectively (HR, 0.18; 95% CI, 0.06 to 0.47). Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients, respectively. CONCLUSION Adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Efficacy outcomes with durvalumab were similar to those reported for other anti–programmed cell death-1/programmed cell death ligand-1 agents. However, the results of secondary analyses suggest a potential role for PARP inhibition in patients with UC harboring HRRm.

Background: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival. Objective: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups. Design, setting, and participants: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC. Intervention: Patients were randomized 1:1:1 to lenvatinib 20mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment. Outcome measurements and statistical analysis: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1. Results and limitations: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75 % target-lesion reduction by 6 mo had a 24-mo OS probability of 91.7 %. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4 % vs 28.8 %) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified. Conclusions: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS. Patient summary: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a ''complete response'' or had their tumors shrunk by >75 % within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

Introduction: Topotecan is approved as second-line treatment for smal l ce l l lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support dis-ialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus iri-notecan in this setting. We tested dinutuximab/irinotecan versus irinotecan or topotecan as second-line therapy in relapsed/refractory (RR) SCLC. Materials and methods: Patients with RR SCLC and Easter n Cooperative Oncolog y Group performance status 0-1 were randomized 2:2:1 to receive dinutuximab 16-17.5 mg/m(2) intravenous (IV)/irinotecan 350 mg/m(2) IV (day 1), irinotecan 350 mg/m(2) IV (day 1), or topotecan 1.5 mg/m(2) IV (days 1-5) in 21-day cycles. The prima r y endpoint was overa l l survival (OS); seconda r y endpoints were progression-free survival (PFS), objective response rate (ORR; complete response [CR] + partial response [PR]), and clinical benefit rate (CBR; CR + PR + stable disease). Safety/tolerability were also assessed. Results: A total of 471 patients were randomized to dinutuximab/irinotecan (n = 187), irinotecan (n = 190), or topotecan (n = 94). Age, sex, performance status, prior therapies, and metastatic disease sites were similar between groups. Survival and response rates were not improved for patients receiving dinutuximab/irinotecan versus those receiving irinotecan or topotecan (median OS 6.9 vs 7.0 vs 7.4 months [p = 0.3132]; median PFS 3.5 vs 3.0 vs 3.4 months [p = 0.3482]; ORR confirmed 17.1% vs 18.9% vs 20.2% [p = 0.8043]; and CBR 67.4% vs 58.9% vs 68.1% [p = 0.0989]), respectively. Grade 3/4 adverse events (>= 5% receiving dinutuximab/irinotecan) included neutropenia, anemia, diarrhea, and asthenia. Conclusions: Dinutuximab/irinotecan treatment did not result in improved OS in RR SCLC versus irinotecan alone. Irinotecan administered every 21 days demonstrated comparable activity to topotecan administered daily x 5 every 21 days.

BACKGROUND Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear. METHODS In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated. RESULTS A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P = 0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P = 0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels. CONCLUSIONS Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib. (Funded by Eisai and Merck Sharp and Dohme; CLEAR ClinicalTrials.gov number, NCT02811861.).

Background Cosibelimab is a high affinity, fully-human IgG1 monoclonal antibody that directly binds to programmed death ligand-1 (PD-L1) and blocks its interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors to restore an anti-tumor immune response. Cosibelimab has the additional benefit of a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against tumor cells. Study CK-301–101 is a global, multicenter, multicohort trial that is enrolling patients (pts) with select advanced cancers, including pivotal cohorts of pts with metastatic and locally advanced cutaneous squamous cell carcinoma (cSCC) and a cohort of pts with previously untreated advanced non-small cell lung cancer (NSCLC). Methods Eligible pts were aged ≥18 years with an Eastern Cooperative Oncology Group performance status of 0–1. The cSCC cohorts enrolled pts with histologically confirmed metastatic or locally advanced cSCC not amenable to local therapy. The NSCLC cohort enrolled previously untreated NSCLC pts with advanced disease and a PD-L1 tumor proportion score of at least 50%. Pts received a fixed dose of 800 mg cosibelimab administered intravenously every two weeks. Anti-tumor activity was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and were conducted every 8 weeks for the initial 32 weeks on study, and every 12 weeks thereafter. Results As of August 2020, 114 pts (73M/41F, median age 66 years) with diverse tumor types have been enrolled and treated with cosibelimab. Among these pts, 103 (90%) experienced ≥1 treatment-emergent adverse event (AE), 42 (37%) experienced a grade ≥3 AE, and 6 (5%) experienced a grade ≥3 drug-related AE. The most common AEs were fatigue (25%), anemia (21%), rash (18%) and nausea (16%) and the most common drug-related AEs were fatigue (15%) and rash (14%). In 42 cSCC pts evaluable for response, ORR based on investigator assessment of tumor response was 55% (95% confidence interval [CI]: 39, 70), including 5 (12%) complete responses, with 20/23 (87%) responses ongoing and 10 responses ≥6 months in duration as of data cutoff. In 25 NSCLC pts evaluable for response, ORR based on investigator assessment was 44% (95% CI: 24, 65), with 5/11 (45%) responses ongoing and 10 responses ≥6 months in duration. Conclusions Cosibelimab has a predictable and manageable safety profile and demonstrated robust clinical activity in cSCC and NSCLC pts, including durable complete and partial responses. Updated results will be presented. Trial Registration NCT03212404 Ethics Approval The study was approved by an appropriate ethics committee for each participating institution. Informed consent was obtained for all subjects. Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

9017 Background: Although SCLC is highly responsive to initial therapy, most pts relapse < 1 y. Topotecan (T) and irinotecan (I) are used in 2LT of SCLC; however, treatment response is low: ≤10-25% and median survival is ~4-5 months. Preclinical studies support GD2 as an SCLC target. This study evaluated the combination of D+I vs. I alone or T alone in 2LT of SCLC pts. Methods: Pts with RR SCLC, Eastern Cooperative Oncology Group 0-1, were randomized 2:2:1 to receive D 16-17.5 mg/m 2 intravenously (IV) plus I 350 mg/m 2 IV (Day 1 q21d), I 350 mg/m 2 IV (Day 1 q21d), or T 1.5 mg/m 2 IV (Days 1-5 q21d). Randomization was stratified by duration of response to prior platinum therapy. Primary endpoint was overall survival (OS) in pts treated with D+I vs. I alone and was analyzed using stratified log-rank test and COX regression. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate, ORR + stable disease (CBR). Safety was assessed. Results: 471 pts were randomized to D+I (n = 187), I (n = 190), or T (n = 94). Baseline characteristics were balanced (24.2% women; mean ± SD age 61.6 ± 8.7 y). Median OS was similar in pts receiving D+I (6.9 [3.5,10.9] months) vs. I alone (7 [3.6,13.1] months) (HR [95% CI]: 1.12 [0.9,1.4]; P = 0.3132) or T alone (7.4 [3.8,12.8] months) (HR [95% CI]: 1.05 [0.8,1.37]; P = 0.7233). Median PFS was similar in pts receiving D+I (3.5 [1.5,6.2] months) vs. I (3 [1.4,5.7] months) or T (3.4 [1.6, 6.1] months) alone. ORR was similar in pts receiving D+I (17.1%) vs. I (18.9%) or T (20.1%) alone. CBR was similar in pts receiving D+I (67.4%) vs. I (58.9%) or T (68.1%) alone. Grade 3 or higher adverse events were experienced by 77% D+I, 69.5% I, and 86.4% T pts. Conclusions: Treatment with D+I was not superior to established 2LT for RR SCLC. Exploratory analyses are ongoing to evaluate GD2 expression in circulating tumor cells, select protein biomarkers, and any correlative impact on observed response. Clinical trial information: NCT03098030.

EGFR tyrosine-kinase inhibitors (TKIs) are used as targeted therapeutics for the treatment of advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. EGFR C797S is common causes of acquired resistance to third-generation TKIs. There is wide-spread opinion that resistance-conferring mutation present even in a small proportion of cancer cells before the start of therapy could potentially predict poor response to a targeted drug. In our study, we tested whether C797S can be found in previously untreated NSCLCs. We analyzed DNA samples extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue sections of 470 lung adenocarcinoma patients, including 235 samples with activating EGFR mutations. Screening was performed using highly sensitive droplet digital PCR assay. No tumor samples with baseline C797S were identified. C797S does not occur in TKI-naïve NSCLCs and provide evidence that screening for this mutation before TKIs administration may not be necessary.

e13109 Background: There is a little information of correlation between EGFRm rate in cytology and plasma samples in Russian NSCLC population. The interim analysis of the study aimed to evaluate the prevalence and types of EGFR mutations in paired cytology and plasma samples in treatment-naive patients with advanced NSCLC. Methods: ORTUS is a multicenter, non-interventional, prospective study to determine EGFR mutations rate in treatmentnaive Russian patients with advanced NSCLC. ClinicalTrials.gov identifier: NCT02321046. The study enrolled 426 patients in stage IIIB / IV of NSCLC. Interim analysis covered the data of 214 cytology verified patients (mean age - 62.6 (range 32-86) years, 58,4% of men) with EGFRm test results in paired cytology and ctDNA samples. 99.5% cases were adenocarcinoma. The proportion of non-smokers/smokers/exsmokers was 46.3%/36%/17.8% respectively. Stage IV disease was in 81% of cases; 84.1% of patients had symptoms. DNA isolation performed using QIAamp DNA FFPE Tissue Kit for cytology and Qiagen Circulating Nucleic Acid Kit for ctDNA according to the manufacturer’s instructions. EGFR gene mutations were analyzed using THerascreen RGQ EGFR PCR Kit in cytology samples and RGQ Plasma EGFR PCR kit in plasma (Qiagen). Results: EGFRm was identified in 17,8% cytology samples (38/214) that is close to 20,2% (1759/8716) in Russian tissue EGFRm study (Imyanitov et al., 2016). 10,3% of paired ctDNA samples were EGFRm positive. Sensitivity and specificity for ctDNA were 42.1%, and 97.1% respectively. The EGFRm rate was 3,9% and 2,6% in smokers, 5,3% and 0% in ex-smokers and 33,3% and 21,2% in nonsmokers in cytology and plasma samples respectively. EGFRm rate and concordance between cytology and ctDNA are presented in a table. EGFRm in ctDNA were detected more frequently in M1a/b groups (p = 0,028). Conclusions: Cytology samples are appropriate for EGFRm testing in NSCLC patients in comparison with tumor tissue ones. High tumor burden (positive metastatic status) is an important factor for successful mutation analysis in ctDNA. [Table: see text]

Identification of prognostic molecular markers of breast cancer is extremely important. The spreading out of the primary breast tumour cells to the lymphatic system is at the forefront of symbolising the first signs of distant organ metastasis. Deregulated genes in breast cancer tissues that spread to lymph nodes may show early predictive molecular markers. In the present study, we selected five microRNAs, which play a key function in the invasion-metastasis cascade. We investigated the levels of microRNAs in 80 paired samples of BC and matched adjoining tissues, and we examined the potential relationships between microRNA levels and positive lymph node status. Our results attest that three microRNAs (miR-21, miR-155, miR-222) were significantly up-regulated, whilst miR-205 was substantially down-regulated in BC tissues in relation to normal adjoining tissues in a heterogeneous patient cohort. The high levels of two microRNAs, miR-155 and miR-222, showed a statistical relation with the positive lymph node status, especially in patients that had triple negative BC. Conversely, miR-155 was substantially down-regulated in tumour tissues of patients who received preoperative neoadjuvant chemotherapy (NAC) compared with tumour tissues of patients without NAC in cohorts sub-classified to lymph node positive status. Our findings show evidence that the miR-155 and the miR-222 can be defined as molecular markers in regards to cancer patients to prognosticate spread to the lymph node. They also showed that the miR-155 could have crucial significances in BC treatment.

MDM2 inhibitors are promising anticancer agents that induce cell cycle arrest and tumor cells death via p53 reactivation. We examined the influence of Mycoplasma hyorhinis infection on sensitivity of human lung carcinoma cells NCI-H292 to MDM2 inhibitor Nutlin-3. In order to unveil possible mechanisms underlying the revealed effect, we investigated gene expression changes and signal transduction networks activated in NCI-H292 cells in response to mycoplasma infection.