Gemcitabine Cisplatin Research Articles

Efficacy of cisplatin-gemcitabine-durvalumab in patients with advanced biliary tract cancer experiencing early vs late disease relapse after surgery: a large real-life worldwide population.

In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial. The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS). A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]. Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC.

Effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk upper tract urothelial carcinoma: a retrospective, real-world study.

Upper tract urothelial carcinoma (UTUC) is a rare subset of urothelial cancers with poor prognosis. No consensus exists on the benefit of adjuvant immunotherapy for patients with UTUCs after nephroureterectomy with curative intent and the existing studies are limited. Herein, this study aimed to evaluate the effectiveness and safety of adjuvant treatment of tislelizumab with or without chemotherapy in patients with high-risk UTUC. A retrospective study was conducted on 63 patients with high-risk UTUC who received tislelizumab with or without gemcitabine-cisplatin (GC) chemotherapy regimen after surgery between January 2020 and December 2022. Data on demographic and clinical characteristics, surgical, outcomes, prognostic factors, and safety were collected and analyzed. Among the 63 patients with high-risk UTUC, the median age was 66years (interquartile range 57-72), with 33 (52%) being male. The majority of patients with staged pT3 (44%) and pN0 (78%) disease. Fifty-one patients (81%) received tislelizumab plus GC chemotherapy, and 12 (19%) were treated with tislelizumab monotherapy. After the median follow-up of 26months (range 1-47), 49 (78%) patients achieved stable disease. The 2-year disease-free survival (DFS) and 2-year overall survival were 78.68% (95% CI: 60.02-87.07%) and 81.40% (95% CI: 68.76-89.31%), respectively. The cycles of GC chemotherapy were independent prognostic factors for survival, with higher DFS (hazard ratio = 0.68, 95% CI, 0.50-0.93; p = 0.016) observed in the subgroup undergoing ≥ 3 cycles versus < 3 cycles of GC chemotherapy. Fifty-eight patients (92%) experienced at least one treatment-related adverse event (TRAE), with grade 3-4 TRAEs occurring in 13%. The most common grade 3-4 TRAEs were decreased white blood cells, thrombocytopenia, and ulcers. The study demonstrates promising clinical benefits and a manageable safety profile of the tislelizumab-based adjuvant regimen for patients with high-risk UTUC. This suggests that adjuvant immunotherapy represents a potential therapeutic strategy for this population.

Comparison of First-Line Chemotherapeutics and Validation of the EORTC Prognostic Index in Malignant Pleural Mesothelioma: Retrospective Single-Centre Experience.

To evaluate the efficiency of pemetrexed cisplatin in comparison with gemcitabine cisplatin and to validate the EORTC (European Organisation for Research and Treatment of Cancer) prognostic score in combination chemotherapy treatment for malignant pleural mesothelioma. An observational study. Place and Duration of the Study:Department of Oncology, Dicle University Hospital, Diyarbakir, Turkiye, from October 2000 to November 2017. Malignant pleural mesothelioma (MPM) patients with EORTC score 0- were recruited. Factors affecting the prognosis of the disease and the effectiveness of first-line treatment were retrospectively analysed. EORTC prognostic score was calculated with a cut-off and survival analyses were used by the Kaplan-Meier method. Log-rank and univariable Cox regression tests were used to search for prognostic factors' impact on survival. Patients who received gemcitabine cisplatin treatment had a median progression-free survival (PFS) of 9 months, while those who received pemetrexed cisplatin therapy had a median PFS of 7 months. Median overall survival (OS) was 17 months in the gemcitabine cisplatin group and 18 months in the pemetrexed cisplatin group (p = 0.051). When the low-risk group was compared with the high-risk group, the median OS was found to be statistically significant (p = 0.009). The EORTC prognostic score, which is used for prognostic prediction in the period when pemetrexed is not utilised in the treatment of MPM, accurately predicts prognosis subsequent to the administration of pemetrexed in treatment. In the context of first-line treatment, cisplatin in combination with gemcitabine and cisplatin in combination with pemetrexed demonstrated comparable efficacy with respect to both overall survival and progression-free survival. Chemotherapy, Mesothelioma, Prognosis, Gemcitabine, Progression-free survival.

Treatment Outcomes in Advanced Biliary Tract Cancers: Single Institution Retrospective Analysis

Abstract Purpose Biliary tract cancers (BTCs), particularly gallbladder cancers (GBCs), are prevalent in India. Yet there are limited data on treatment outcomes. To bridge this gap, we performed an analysis of advanced BTC treatment outcomes at our institute, seeking to offer insights into real-world scenario. Materials and Methods This is a retrospective study comprising advanced BTC patients treated at our institute from January 2015 to March 2023. We assessed demographics, treatment approaches, progression-free survival (PFS), overall survival (OS), and associated toxicities. Results Of the 411 patients analyzed, the majority were GBC (67.3%, n = 277), while the rest were cholangiocarcinoma (CCA) (32.6%, n = 134). The median age of study population was 56 years. Palliative chemotherapy was administered in 85% (n = 349) of all patients. Gemcitabine–cisplatin doublet was the most commonly used chemotherapy regimen (80.2%, n = 280). Platinum doublets yielded higher response rates compared with single-agent/nonplatinum chemotherapy (60 vs. 30%, n = 133). The median PFS was 4 months. The median OS was 8 months with platinum doublets and 5 months with single-agent/nonplatinum chemotherapy (hazard ratio [HR]: 0.60, 95% confidence interval: [CI] 0.43–0.84, p = 0.0001). OS was no different based on the type of platinum agent used. Patients receiving multiple lines of treatment lived longer compared with those who received single line only (14 vs. 6 months, respectively, HR: 0.36, 95% CI: 0.28–0.45, p &lt; 0.0001). Significant prognostic factors for OS were treatment with chemotherapy, platinum doublets, platinum exposure in first line, and treatment beyond first line. Grade 3 or 4 adverse effects seen were anemia (13.9%, n = 36), vomiting (4.2%, n = 11), diarrhea (3.4%, n = 9), thrombocytopenia (3.4%, n = 9), and febrile neutropenia (3.1%, n = 8). Conclusion This analysis confirms that chemotherapy is beneficial for advanced BTC. Platinum-based doublets are more effective than single agents. There is no significant difference between cisplatin and oxaliplatin. Patients who received multiple lines of treatment had better OS.

TOURMALINE: A phase 3b study of durvalumab with gemcitabine-based chemotherapy regimens in advanced biliary tract cancer.

TPS4188 Background: In the Phase 3 TOPAZ-1 study (NCT03875235), durvalumab plus gemcitabine + cisplatin (GC) significantly improved overall survival (OS) versus placebo + GC in participants with advanced biliary tract cancer (aBTC) with a manageable safety profile. To expand on TOPAZ-1, there is a need to further assess the safety and efficacy of durvalumab in combination with other gemcitabine (G)-based chemotherapy regimens used in aBTC, and in a more diverse population to reflect real-world clinical practice. Methods: TOURMALINE (NCT05771480) is a Phase 3b, single-arm, multicenter, international study. Approximately 140 adults with aBTC (intra- or extra-hepatic cholangiocarcinoma, gallbladder or ampulla of Vater carcinoma) will be enrolled. Key inclusion criteria include unresectable disease (advanced, metastatic), WHO/ECOG PS of 0–2, and no prior systemic therapy. Key exclusion criteria include any prior immune-mediated therapy and history of another primary malignancy. Participants will receive durvalumab 1500 mg IV plus an investigator-selected, G-based background chemotherapy; durvalumab will be administered Q3W when combined with a G-based chemotherapy Q3W (8 cycles of durvalumab) except for when combined with GC + S-1 Q2W, in which case durvalumab will be administered Q4W (4 cycles of durvalumab/8 cycles of chemotherapy). G-based chemotherapy will consist of G monotherapy, GC (for WHO/ECOG PS 2 participants only), G + oxaliplatin, G + carboplatin, GC + S-1, G + S-1, and GC + albumin-bound paclitaxel. Following the treatment period, durvalumab Q4W +/- chemotherapy (except for paclitaxel) may continue, at the investigator’s discretion, until discontinuation criteria are met. The primary endpoint is the incidence of Grade 3 or 4 adverse events, assessed by the investigator to be possibly related to any study treatment within 6 months after initiation of durvalumab. Secondary endpoints include OS, objective response rate, progression-free survival, and duration of response. Enrollment is ongoing and planned in France, Germany, United States, Spain, Italy, Japan, South Korea, and Singapore. Clinical trial information: NCT05771480 .

Characterization of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node–only metastatic urothelial carcinoma from the CheckMate 901 trial.

4509 Background: In the CheckMate 901 trial, combination nivolumab (NIVO) + gemcitabine-cisplatin (GC) demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with compelling objective response rates (ORR; 57.6% with NIVO+GC vs 43.1% with GC alone) and deep, durable complete responses (CR; 21.7% with NIVO+GC vs 11.8% with GC alone) in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC). Lymph node (LN)-only metastatic disease is a favorable prognostic factor in pts with mUC and a subset of pts achieve durable disease-free, treatment-free survival with GC +/- surgical consolidation. We conducted a post hoc analysis to characterize the subset of pts with CR, with further analysis of pts with LN-only mUC. Methods: In the global, open-label, randomized, phase 3 CheckMate 901 (NCT03036098) trial, cisplatin-eligible pts received NIVO 360 mg + GC every 3 wk for ≤6 cycles followed by NIVO 480 mg every 4 wk until disease progression/unacceptable toxicity or up to a maximum of 2 yrs, or GC every 3 wk for ≤6 cycles. Primary endpoints were OS and PFS by blinded independent central review (BICR). ORR per BICR and safety were exploratory endpoints. These post hoc analyses evaluated treatment outcomes in complete responders and in pts with LN-only disease. Results: Of the 608 pts randomized, 102 (16.8%) achieved a CR. Baseline disease characteristics of these pts are shown in the Table. As pts with LN-only mUC were enriched in the CR group, additional analysis of this subgroup was performed. Of all randomized pts, 54 treated with NIVO+GC and 56 treated with GC had LN-only mUC. In these pts, the ORR and CR rate was 81.5% (95% CI 68.6-90.7) and 63.0% versus 64.3% (50.4-76.6%) and 33.9% for NIVO+GC and GC, respectively. Median OS (95% CI) in LN-only pts was 46.3 (24.0-NE) mos with NIVO+GC vs 24.9 (21.4-29.9) with GC (HR, 0.58, 95% CI 0.34-1.00), and median PFS (95% CI) was 30.5 (9.6-NE) mos with NIVO+GC vs 8.8 (7.5-10.9) mos with GC (HR 0.38, 95% CI 0.22-0.66). Conclusions: NIVO+GC generated deep responses in CheckMate 901 with a fixed duration of chemotherapy and up to 2 years NIVO. Exploratory characterization of pts with CR identified a group of pts enriched with LN-only disease.In pts with LN-only mUC, NIVO+GC induced durable disease control and clinically meaningful improvements in OS and PFS vs GC alone. These results provide additional support for NIVO plus cisplatin-based chemo as a first-line treatment option for pts with mUC. Clinical trial information: NCT03036098 . [Table: see text]

Four-year overall survival follow-up and dynamic EBV titer analysis of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (r/m NPC).

6039 Background: In October 2023, the US FDA approved toripalimab in combination with Gemcitabine-Cisplatin (GP) as first-line treatment for recurrent or metastatic (r/m) NPC based on the results of JUPITER-02 study (NCT03581786). Here we report the results of four-year overall survival (OS) follow-up and dynamic EBV DNA copy number and its correlation with clinical outcome. Methods: Patients with r/m NPC (n=289) were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with GP once every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG performance score (0 vs. 1) and extent of disease (recurrent vs.primary metastatic). The primary endpoint was progression free survival by an independent review committee. Secondary endpoints included OS and safety. Exploratory endpoints included dynamic blood EBV DNA copy number and its correlation with clinical efficacy. Results: By the cutoff date of January 9, 2024, 50 months after the last patient was enrolled, 150 deaths were recorded. Compared with the results from the final OS analysis, consistent survival improvement was observed for toripalimab over placebo: HR=0.61 (95% CI: 0.44-0.85), nominal p=0.0027. The median OS was not yet reached in the toripalimab arm and was 33.7 months in the placebo arm. The 5-year OS rates were 52.0% in the toripalimab arm, and 33.9% in the placebo arm. Among patients with detectable baseline EBV DNA copy number and at least one EBV result after study treatment, significantly more patients from the toripalimab arm had EBV DNA copy number decreased to undetectable level than those in the placebo arm, 96.3% vs. 84.5%, p= 0.004. In addition, significantly less patients experienced EBV DNA copy number rebound in the toripalimab arm than in the placebo arm after the initial reduction, 36.5% vs, 57.4%, p=0.002. The median time from the lowest EBV DNA copy number to the rebound was 20.5 vs. 6.0 months in the toripalimab and placebo arms respectively. The rebound also preceded investigator-assessed disease progression by a median of 1.9 months in the toripalimab arm. Conclusions: The combination of toripalimab and chemotherapy showed long term survival benefit than chemotherapy alone with a 5-year OS rate at 52%. EBV DNA copy number might be used to monitor clinical response and predict disease progression. Clinical trial information: NCT03581786 .

Is the gemcitabin cisplatin doublet the optimal induction chemotherapy for non-Asian patients with NPC? Insights from a northeastern Moroccan cohort.

e18057 Background: According to the latest guidelines for NPC, induction chemotherapy followed by concomitant chemoradiation therapy (CCRT) is recommended as the preferred standard of care for patients with locally advanced nasopharyngeal carcinoma (stage III-Iva). However, the optimal regimen for induction chemotherapy (IC) in patients with locally advanced NPC remains uncertain. Methods: We conducted a retrospective study between January 2016 and October 2022 at the "CHU Hassan II" Oncology Hospital in Fes, Morocco, to compare the efficacy and tolerability of two platinum-based induction therapy regimens: cisplatin gemcitabine (GC) and cisplatin doxorubicin (DP), in the treatment of newly diagnosed locally advanced NPC. The main objectives of this study were to compare the efficacy including objective response rates (ORR), PFS ,OS and safety. Results: After eligibility assessment, we included 105 cases (62 patients in the DP group and 43 in the GC group), including 65 men and 40 women, with a mean age of 49.5 years (range = 19-79years) and a Karnofsky score ranging from 87% to 100%. 34% of patients were diagnosed at stage IVA. In the DP group, 3% of patients (2 out of 62) achieved a complete response CR, 60% achieved a partial response PR,25% remained stable SD and 19% experienced progression. In the GC group, 2% of patients (1 out of 43) achieved a CR, 39.5% achieved a PR, 39.5% remained stable, and 19% experienced progression. A statistically significant difference in PR was observed between the two groups (p = 0.028) ,and the difference in terms of progression is approaching the limit of significance (p=0,06) after a median follow-up of 27 months (5,3 -82). The 2-year progression-free survival (PFS) was 70% in the DP group compared to 80% in the GC group; the 2-year overall survival (OS) was 75% in the DP group and 90% in the GC group. No significant survival difference was observed between the two groups Patients in the DP group exhibited less grade 3-4 thrombocytopenia but more grade 3-4 leukopenia and neutropenia compared to the GC group. Conclusions: In patients with locally advanced nasopharyngeal carcinoma, GC-based induction chemotherapy demonstrated superior ORR over the DP regimen with acceptable toxicities. Further studies are needed to validate these results.

Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004.

4516 Background: Immunotherapy in the perioperative setting of MIUC appears promising. The AURA trial (NCT03674424) investigated the addition of avelumab to neoadjuvant dose-dense MVAC (ddMVAC) or cisplatin-gemcitabine (CG) respectively, followed by surgery in the cisplatin-eligible cohort. The primary endpoint was previously reported with high pathological complete response (pCR) rates with each cisplatin-based regimen. In the cisplatin-ineligible cohort, pts were randomized to neoadjuvant A alone or in combination with paclitaxel-gemcitabine (PG) followed by surgery. Avelumab monotherapy showed encouraging pCR but the addition of PG did not provide any benefit. Here, we report the survival data from cisplatin-eligible and ineligible cohorts of the AURA trial. Methods: In the cisplatin-eligible cohort, 79 pts were randomly assigned to the ddMVAC-A (n=39) or CG-A (n=40) groups. In the cisplatin-ineligible cohort, 58 pts were randomly assigned to the PG-A (n=29) or A (n=29) groups. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method at 12 months and 36 months for the overall cohort and by subgroups. Results: Median follow-up was 33 months and 45 deaths were reported. In the cisplatin-eligible cohort, 12-month DFS was 92% (95% CI, 83-96%) and 36-month DFS was 72% (95% CI, 57-83%). For ddMVAC-A group: 97% and 77%, respectively. For CG-A group: 86% and 68%. Overall, 12-month OS was 89% (95% CI, 80-95%) and 36-month OS was 73% (95% CI, 61-83%). For ddMVAC-A: 95% and 87%. For CG-A: 84% and 61%. Among the ypT0N0 pts, no events were registered within 12 months of follow-up showing a DFS rate of 100% for both arms. At 36 months no events were reported for pts treated with ddMVAC-A and two for CG-A showing DFS rates of 100% and 78% respectively. In the cisplatin-ineligible cohort, 12-month DFS was 60% (95% CI, 46-72%) and 12-month OS was 71% (95% CI, 57-81%). For PG-A: 52% and 67%. For A: 68% and 75%. Among the ypT0N0 pts, no DFS events occurred within 12 months. Data for 36-month are not yet mature. Overall, the main cause of death was disease progression (73%). Conclusions: The addition of neoadjuvant avelumab to cisplatin-based chemotherapy results in a high DFS and OS at 12 and 36 months respectively, especially in pts with complete response to neoadjuvant treatment. Combination with ddMVAC regimen offers robust activity. Cisplatin-ineligible pts had lower survival outcomes with no benefit of PG addition. Clinical trial information: NCT03674424 . [Table: see text]

Abstract 4025: A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis

Abstract Immune checkpoint inhibitors (ICIs) have been widely used in recurrent or metastatic nasopharyngeal carcinoma (NPC), but the addition of ICIs to chemoradiotherapy in locoregionally advanced (LA) NPC requires further investigation. We conducted a phase II, single-arm trial to evaluate the efficacy and safety of neoadjuvant gemcitabine, cisplatin (GP) plus tislelizumab followed by concurrent chemoradiotherapy (CCRT) in LA-NPC. All participants received 3 cycles of GP chemotherapy plus tislelizumab (200 mg) followed by 3 cycles of cisplatin-based CCRT. The primary endpoint was the clinical complete response rate (CR) after neoadjuvant chemoimmunotherapy (NAT). The secondary endpoints include pathological CR rate, progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), etc. Pretreatment blood samples and paired (pre-/post-NAT) tissue biopsies were collected to perform full-spectrum peripheral T-cell profiling, PD-L1 and tertiary lymphoid structures (TLS) staining. Among all 63 participants, the CR rate after NAT reached 41.3% (95% CI, 28.8%-53.8%), far exceeding our hypothesized CR rate of 22%. The objective response rate (ORR) and pCR rate after NAT were 88.9% (95% CI, 80.9% to 96.9%) and 74.6% (95% CI, 62.1% to 84.7%), respectively. As of July 15th, 2023, after the median follow-up of 25 months, the 2-year PFS and OS were 98.4% and 100%. The incidence of grade 3-4 immunotherapy-related adverse events was 1.6%. The compliance of CCRT was not compromised. Patients who achieved CR had significantly more circulating CD4+ and CD8+ effector memory T cells (Tem), regulatory T cells (Treg) and follicular helper T cells (Tfh). The peripheral abundance of LAG3+ Tem and Tfh were independently predictive of NAT response. The number and maturation of TLS significantly increased after NAT in the CR group, but not in the Non-CR group. GP chemotherapy plus tislelizumab followed by CCRT was highly therapeutic and safe in treating LA-NPC, further randomized phase III studies are awaited. Citation Format: Xiao-Yun Li, Si-Yi Xie, Qiu-Yan Chen, Hai-Qiang Mai, Lin-Quan Tang. A phase II trial of neoadjuvant gemcitabine, cisplatin plus tislelizumab followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Clinical efficacy, safety and the biomarker analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4025.

Clinical and economic effectiveness of using immunotherapeutic drugs in patients with urothelial carcinoma in the healthcare system of the Russian Federation

Aim. To perform pharmacoeconomic evaluation of chemotherapy schemes GC (gemcitabine, cisplatin) and GemCarbo (gemcitabine, carboplatin) in comparison with immunotherapy drugs atezolizumab, pembrolizumab or avelumab in patients with locally advanced or metastatic urothelial carcinoma.Materials and methods. Pharmacoeconomic cost–effectiveness analysis, sensitivity analysis in context of changes of initial model parameters were performed.Results. Literature data analysis allows to make a conclusion of better clinical effectiveness and safety of immunotherapy drugs compared to chemotherapy in patients with urothelial carcinoma. Cost of medications was significantly lower for platinum-based chemotherapy (103,625.61 rubles for GC and 88,733.63 rubles for GemCarbo) compared to a course of immunotherapy (950,092.39 rubles for atezolizumab, 953,340.21 rubles for pembrolizumab, 1,328,999.43 rubles for GC + avelumab). However, the cost of treatment of complications arising during platinum-based chemotherapy was more than 20-fold higher than cost of treatment of immunotherapy complications: 578,853.02 rubles versus 15,336.78– 26,994.52 rubles). Cost–effectiveness analysis favored atezolizumab for which cost–effectiveness ratio was 53,230.69 rubles for 1 month of patient’s life. Atezolizumab had better value than standard 1st line GC chemotherapy by 10,671.80 rubles, as well as immunotherapy courses using pembrolizumab by 9,697.57 rubles and GC + avelumab by 10,824.66 rubles. The highest costs were observed for GemCarbo chemotherapy course: it is 18,522.82 rubles more expensive than atezolizumab course. Sensitivity analysis performed for the cost–effectiveness ratio showed stability of the developed model in regards to increased cost of atezolizumab course up to +18 % and decrease in overall survival with this course up to –15 %.Conclusion. Atezolizumab is a clinically effective and economically justified option for treatment of adults with locally advanced or metastatic urothelial carcinoma and PD-L1 expression ≥5 % in the healthcare system of the Russian Federation.

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies.

Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Application of artificial intelligence (AI) features of nuclear morphology from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in patients with MIBC undergoing cystectomy.

674 Background: BLASST-1 is a multi-center phase II trial evaluating neoadjuvant nivolumab (N) with gemcitabine-cisplatin (GC) for patients (pts) with MIBC undergoing radical cystectomy (RC) (NCT03294304). 41 pts with MIBC (cT2-T4a, N≤1, M0) were enrolled between Feb 2018 and June 2019; (cT2N0 90%, cT3N0 7%, cT4N1 3%). Pts received C (70mg/m2) IV on D1, G (1000mg/m2) on D1, D8, and N (360 mg) IV on D8 every 21 days for 4 cycles followed by RC within 8 wks. The primary endpoint was pathologic downstaging (PaR; ≤pT1N0). Safety, Relapse-free survival (RFS), Progression-free survival (PFS) and biomarker analyses were secondary endpoints. PaR rate was 65.8%, the pCR (≤pT is N0) rate was 49% and there were no safety concerns or delays to RC. Morphometric characteristics of the cell nucleus can be used to assess bladder cancer grading and gain insights into cellular functionalities. In this study, we sought to evaluate the ability of the AI model to identify non-responders to neoadjuvant chemo-immunotherapy. in the BLASST-1 cohort based on computerized image features of nuclear morphology and architecture on pre-treatment transurethral resection of bladder tumor (TURBT) tissues. Methods: Of the 41 pts, we had H&amp;E images available for 34 pts, of which 23 had PaR and 11 did not have PaR and these were classified as responder (R) and non-responder (NR) groups. A machine learning model (U-net) was developed and invoked for tumor segmentation on the H&amp;E images from the BLASST-1 cohort. A second machine learning model (HoVer-Net) was employed to segment and classify individual nuclei. A total of 408 features relating to the textural and spatial arrangement of individual cancer nuclei were extracted. The 17 most significant features, identified through the least absolute shrinkage and selection operator, were used to train a Cox regression model to predict the risk of death using 361 MIBC pts from the Cancer Genome Atlas (TCGA). This Cox model was then applied to assign a risk score to pts in BLASST-1, using a threshold learned from TCGA pts, the individual pts in BLASST-1 were assigned as either low-risk or high-risk. Results: The top identified prognostic features described the textural appearance of individual nuclei with more texture. This model accurately predicted PaR in BLASST-1, with an area under a receiver operating characteristic curve of 0.83. Overall, the pts with the same nuclear angle direction within the tumor tissue had a high chance of response to the neoadjuvant chemo-IO combination in the BLASST-1 trial. Conclusions: A computerized AI model relying on nuclear morphologic and architecture features demonstrated prognostic capability in MIBC within the TCGA dataset and predictive capability for the PaR in the BLASST-1 trial. These findings support further validation studies.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

GCISAVE: A non-comparative randomized phase II study of combination of gemcitabine cisplatin (GCis) +/- avelumab (A) in 1st line treatment for locally advanced or metastatic urothelial bladder carcinoma (MUBC)—GETUG AFU V07.

Characterization of outcomes and genomic alterations (GA) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA).

458 Background: Hepatobiliary cancers comprise a heterogeneous spectrum of invasive carcinomas involving the liver and bile ducts. Due to its rarity, the prognosis and clinical outcomes data are poorly understood. This study aims to provide insight into the response to therapeutic options and GA in patients (pts) with cHCC-CCA. Methods: We conducted a retrospective analysis of clinical outcomes data and GA at MD Anderson (MDA) from 2009 to 2023 in pts with cHCC-CCA. Pt characteristics were compared using Fisher’s exact test and Mann-Whitney U. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier and the log-rank test. Results: 40 pts with cHCC-CCA were analyzed. Hepatitis B and C were the most common etiologies (Table). 25.0% had portal vein tumor thrombus and 72.0% had advanced disease (M1/N1) at diagnosis. Radiographic washout was seen in 55.9%. Elevation of CA19-9, AFP, and both was in 42.5, 57.5, and 30.0%. Cirrhosis at diagnosis was 35.0%. Pts who underwent surgery (n=10) had significant OS benefit (55.6 vs. 14.1 m, p&lt;0.001). Y90 (n=4)/radiation therapy (n=10) provided significant OS benefit in pts who did not undergo surgery (23.3 vs 10.9 m; p=0.012). 34 pts received 1st line systemic therapy: 10 pts received gemcitabine/cisplatin (GC) combined with immunotherapy (GCI): GC + nivolumab (n=5), durvalumab (n=3), or atezolizumab/bevacizumab (AB, n=2). GCI was compared to other regimens (OR, n=24) including chemotherapy alone (GC, FOLFIRI, FOLFOX), HCC-directed therapy alone (AB, lenvatinib, nivolumab), or chemotherapy plus lenvatinib or bevacizumab with mPFS of 7.0 vs. 2.9 m (p=0.014) showing significant PFS benefit. Pts who received GCI trended to better OS compared to OR (18.9 vs. 12.0 m, p=0.380). 2 pts treated with GC+AB had complete responses to date at 36.0 and 14.0 m. Of 31 pts who underwent GA testing, the 2 most frequent GAs were TP53 (38.7%) and TERT (35.5%) mutations. Neither impacted OS: TP53 15.8 vs. 17.6 m (p=0.746); TERT 9.8 vs. 23.3 m (p=0.355). Conclusions: GCI had survival benefit compared to OR in cHCC-CCA. Pts who present with early stage of disease should be evaluated early for surgical resection or maximize local therapy in the case of nonresectable disease to improve survival. [Table: see text]

Mutation-based therapies for intrahepatic cholangiocarcinoma: new options on the horizon

Intrahepatic cholangiocarcinoma (ICC), a rare but rising global malignancy originating from the bile ducts, poses significant challenges in terms of effective treatment and patient outcomes. While surgical excision remains the curative option, its limited efficacy necessitates more therapeutic strategies, including systemic therapies. The management of ICC involves a multidisciplinary approach, with treatment decisions guided by patient-specific and tumor-specific factors. Gemcitabine-cisplatin (GEMCIS) chemotherapy has been a standard first-line therapy, but recent advancements in immunotherapy, particularly the introduction of durvalumab, have provided new hope. Additionally, gene mutation-based therapies, targeting fibroblast growth factor receptors (FGFRs), isocitrate dehydrogenase-1 (IDH1), human epidermal growth factor receptor-2 (HER2), and B-RAF proto-oncogene (BRAF), offer promising prospects for personalized treatment. High-throughput genomic profiling technologies have facilitated the identification of actionable targets and the development of innovative therapeutic approaches. This review summarizes the mutation-based therapies in ICC, including FDA-approved targeted drugs and ongoing clinical trials, highlighting the evolving landscape of ICC treatment.

Gemcitabine/Cisplatin versus docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy in locally advanced nasopharyngeal carcinoma.

Induction chemotherapy followed by concomitant chemoradiation is the standard therapy for patients with locoregionally advanced NPC. There is a limitation of clinical studies that compare different induction regimens. The purpose of this work is to analyze the efficacy of two distinct chemotherapy regimens, docetaxel, cisplatin, and 5-fluorouracil (TPF) and gemcitabine/cisplatin (GP), in treating patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). We analyzed 81 patients initially presented with stage III-IVA NPC from January 2019 to June 2023. Participants were randomized in 1:1 ratio to obtain GP regimen or TPF regimen followed by concurrent CRT. The overall response rate was 97.5% after induction chemotherapy in both groups (In GP arm, 78% of patients achieved complete remission compared to 70% of patients treated with TPF regimen). The satisfactory tumor response to induction chemotherapy was linked with significant enhanced progression free survival [CI (3.37-13.92), HR=2.16, P=0.001] and overall survival [CI (3.717-9.443), HR=1.873, P=0.001]. The GP regimen was both efficacious and well-tolerated. Leucopenia and neutropenia (Grade 3-4) were significantly lower in GP group contrasted to in TPF group. There was no significant difference in the 3-year DFS and OS between GP and TPF protocols.

Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

218P Clinical effectiveness of tislelizumab combined with gemcitabine/cisplatin (GC) versus GC as adjuvant therapy in high-risk muscle-invasive urothelial carcinoma (MIUC): A real-world study

218P Clinical effectiveness of tislelizumab combined with gemcitabine/cisplatin (GC) versus GC as adjuvant therapy in high-risk muscle-invasive urothelial carcinoma (MIUC): A real-world study

Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma

BackgroundNo new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy.MethodsIn this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine–cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine–cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes.ResultsA total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine–cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P=0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine–cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P=0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine–cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine–cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively.ConclusionsCombination therapy with nivolumab plus gemcitabine–cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine–cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.)