Gemcitabine Plus Cisplatin Research Articles

Comparison of first-line treatments for recurrent or metastatic nasopharyngeal carcinoma based on phase 3 randomized clinical trials.

e18012 Background: Guidelines recommend platinum-based chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients. There are a variety of available combination treatment options, however, there is lack of research evaluating their advantages and disadvantages. Therefore, this study aims to compare the efficacy and adverse events (AEs) of the first-line treatment for R/M NPC. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for phase 3 randomized clinical trials (RCTs) in which two first-line treatments for R/M NPC were compared. Among the included trials, progression-free survival (PFS) and overall survival (OS) were calculated using the hazard ratio (HR) and 95% Bayesian confidence interval (95% CrI), while the odds ratio (OR) and 95% CrI were used to evaluate the incidence of severe AEs. The cumulative ranking plot and surface under the cumulative ranking curve (SUCRA) were used to evaluate the rank probability of each regimen. Results: Three trials involving 4 total regimens were included. In terms of PFS, toripalimab plus gemcitabine plus cisplatin (GP) (HR: 0.28; 95% CrI: 0.081-0.98) and camrelizumab plus GP (HR: 0.28; 95% CrI: 0.079-0.96) were significantly superior to fluorouracil plus platinum (PF). In the rank analysis, camrelizumab plus GP was most likely to be the best regimen (SUCRA = 0.81), followed by toripalimab plus GP (SUCRA = 0.80). There was no significant difference among these treatments in terms of OS or AEs. Conclusions: This is the first network meta-analysis comparing the pros and cons of first-line regimens for R/M NPC based on phase 3 randomized clinical trials. Our research showed that toripalimab/camrelizumab plus GP was found to be the most effective treatment regimens for the first-line treatment for R/M NPC in terms of PFS.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Multidisciplinary Treatment of Patients with Progressive Biliary Tract Cancer after First-Line Gemcitabine and Cisplatin: A Single-Center Experience.

Patients with unresectable biliary tract cancer (uBTC) who progress despite first-line gemcitabine plus cisplatin (GC) treatment have limited systemic options with a modest survival benefit. Data are lacking on the clinical effectiveness and safety of personalized treatment based on multidisciplinary discussion for patients with progressing uBTC. This retrospective single-center study included patients with progressive uBTC who received either best supportive care or personalized treatment based on multidisciplinary discussion, including minimally invasive, image-guided procedures (MIT); FOLFIRI; or both (MIT and FOLFIRI), between 2011 and 2021. Ninety-seven patients with progressive uBTC were identified. Patients received best supportive care (n = 50, 52%), MIT (n = 14, 14%), FOLFIRI (n = 19, 20%), or both (n = 14, 14%). Survival after disease progression was better in patients who received MIT (8.8 months; 95% CI: 2.60-15.08), FOLFIRI (6 months; 95% CI: 3.30-8.72), or both (15.1 months; 95% CI: 3.66-26.50) than in patients receiving BSC (0.36 months; 95% CI: 0.00-1.24, p < 0.001). The most common (>10%) grade 3-5 adverse events were anemia (25%) and thrombocytopenia (11%). Multidisciplinary discussion is critical for identifying patients with progressive uBTC who might benefit the most from MIT, FOLFIRI, or both. The safety profile was consistent with previous reports.

Interim analysis results of gut microbiota in patients with unresectable cholangiopancreatic cancer: SCRUM-Japan MONSTAR-SCREEN.

733 Background: MONSTAR-SCREEN prospectively assessed the gut microbiota of 2000 patients (pts) with advanced solid cancer at 31 Japanese institutions. Here, we report the interim analysis results of the correlation between gut microbiota and the efficacy of first-line chemotherapy in pts with unresectable pancreatic cancer (PC) and bile tract cancer (BTC). Methods: We analyzed unresectable 205 PC and 83 BTC pts with clinical data as data cut-off on April 30, 2021, and 16S ribosome analysis results of stool samples. Among PC pts, 133 and 40 were treated with GnP (gemcitabine (GEM) plus nab-paclitaxel) and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin), respectively. Among BTC pts, 32 and 33 were treated with GC (GEM plus cisplatin) and GCS (GEM, cisplatin, plus S-1), respectively. Pts with an above-median overall survival (OS) were defined as long-term survivors (LTS), and those with below-median OS and OS events were defined as short-term survivors (STS). We compared the alpha diversity index (ADI) of LTS and STS, and identified potential microbial biomarkers of LTS, STS, responders, and non-responders to first-line chemotherapy according to RECIST version 1.1, by linear discriminant analysis effect size (LEfSe). In each cohort, the top three microbiota with linear discriminant analysis scores of ≥ 3.0 were considered significant. Results: The median OS of PC and BTC pts was 13.5 and 15.9 months, respectively. In PC pts, no significant difference was noted in the ADI between LTS (n=20) and STS (n=40). In BTC pts, the ADI of LTS (n=10) was significantly higher than that of STS (n=20) in the Shannon index. LEfSe analysis in PC pts revealed that Burkholderiales and Sutterellaceae were predominant in LTS, while Lactobacillaceae was, in STS. In PC pts, Brachyspiraceae and Erysipelotrichales were predominant in responders (n=67), while Enterococcaceae and Lactobacillaceae were, in non-responders (n=137). In BTC pts, Peptostreptococcaceae, Fusobacteriaceae, and Clostridiaceae in LTS; Cardiobacteriaceae, Prevotellaceae, and Actinobacteriota in responders (n=24); and Bacilli in non-responders (n=59) were overrepresented. Conclusions: This interim analysis identified potential biomarkers of the gut microbiota that may contribute to the prognosis and efficacy of chemotherapy in pts with unresectable PC and BTC. The results of this analysis will be validated in the primary analysis.

Tumor volume reduction after induction chemotherapy with gemcitabine plus cisplatin in nasopharyngeal carcinoma.

To evaluate the tumor volume reduction after induction chemotherapy (IC) with gemcitabine plus cisplatin (GP) and to build prediction models for tumor volume reduction in nasopharyngeal carcinoma (NPC). NPC patients who received GP IC were retrospectively enrolled. The gross tumor volume of the nasopharynx and lymph nodes (GTVnx and GTVnd) were contoured before and after IC. Univariate and multivariate analyses were performed to identify associated factors. Nomogram models were constructed to predict the possibility of tumor volume reduction. A total of 192 patients were enrolled. The mean relative volume reduction for GTVnx and GTVnd was 29.66% and 31.75%, respectively. The volume reduction of GTVnx and GTVnd had a weak association (r = 0.229, p < 0.001). For GTVnx volume reduction, pre-treatment neutrophil count (p = 0.043), lymphocyte count (p = 0.026), LDH level (p = 0.005), and BMI (p = 0.020) were independently associated factors. For GTVnd volume reduction, pre-treatment EBV-DNA (p = 0.029), GTVnd volume (p < 0.001), eosinophil count (p = 0.043), NLR (p = 0.039), LDH level (p = 0.026), and serum potassium level (p = 0.027) were independently associated factors. For the GTVnx nomogram model, areas under the receiver-operating characteristic curve (AUC) were 0.702 and 0.698 for the training and validation cohorts, respectively. For the GTVnd nomogram model, the AUC was 0.872 and 0.758 for the training and validation cohorts, respectively. Tumor volumes reduce significantly after GP induction chemotherapy. Nomogram models for predicting the possibility of tumor volume reduction are built.

Effects of Camrelizumab Combined with First-Line Chemotherapy on Serum SCC, VEGF Levels, and Adverse Reactions in Patients with Advanced Squamous Cell Carcinoma of the Lung.

To study the effects of camrelizumab accompanied by first-line chemotherapy on serum SCC, VEGF levels, and adverse reactions in people undergoing advanced lung squamous cell carcinoma. Data sources of the study subjects were 60 people suffering from advanced squamous cell carcinoma of the lung hospitalized from January 2018 to October 2019. They were assigned to two groups, including the control group and the observation group in a random manner, and each consisted of 30 patients. Those in the observation group received camrelizumab (SHR-1210), and gemcitabine plus cisplatin (GP) chemotherapy were treated in the control group. Finally, according to the results, we compare the data of patients in both groups so as to find out the similarities and differences. Among them, the effective efficiency of clinical treatment in the control group reached 36.67%, and that in the observation group reached 56.67%. Intuitively, it can be concluded that the control group showed lower results than the observed group. The observed group turned out to have higher periodic survival and progression free survival (PFS) of patients than the other group. During and after the cycle treatment, the data of SCC and VEGF were reduced to some extent, but the control group appeared to have a more evident reduction rate than the other group. SHR-1210 combined with chemotherapy has a considerable effect in practical application and has excellent clinical performance.

88P Sintilimab plus anlotinib as second-line therapy for metastatic or recurrent gallbladder carcinoma (GBC): A single-arm, phase II study

Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC), but its effectiveness remains to be improved. PD-1 blockade and chemotherapy have demonstrated important therapeutic advantages in BTC (TOP-AZ). Further, the addition of PD-1 to anlotinib has improved the clinical results in the second-line therapy for additional carcinomas, including cervical cancer and HCC, for which therapeutic options have been limited. The effectiveness and safety of sintilimab plus anlotinib in treating metastatic or recurrent GBC are being evaluated in this study.

Phase 1b clinical trial of pucotenlimab (HX008), a novel anti-PD-1 monoclonal antibody, combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer.

BackgroundPucotenlimab, also called HX008, is a humanized anti-PD-1 antagonist IgG4 mAb. It blocks programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1), and programmed death ligand-2 (PD-L2). In the CBCSG 006 trial, gemcitabine plus cisplatin (GP) has shown impressive antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of pucotenlimab when combined with GP in patients with mTNBC in the first-line setting.MethodsEligible patients with mTNBC with ≥6 months of DFI (disease-free interval) who have never received antitumor therapy for metastatic disease were screened. Participants received pucotenlimab at 3 mg/kg (d1, q3w) plus gemcitabine at 1,250 mg/m2 (d1, 8, q3w) and cisplatin at 75 mg/m2 (d1, q3w). Eligible patients received up to six cycles of pucotenlimab along with GP chemotherapy, while pucotenlimab could be maintained until disease progression or unacceptable toxicity occurred or withdrawal of informed consent. This study was registered in China under registration number CTR20191353.ResultsBetween July 2019 and March 2020, 31 patients were enrolled in this study. The median age was 50 (range 28–68) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other six (19.4%) experienced stable disease (SD). As of 4 August, the median progression-free survival (PFS) was 9.0 months (95% CI, 6.2–9.2). The most common grade 3 or 4 treatment-related adverse events included neutropenia (74.1%), anemia (35.5%), thrombocytopenia (32.3%), hypocalcemia (9.7%), hypokalemia (9.7%), and alanine aminotransferase increased (6.5%). There were no treatment-related deaths.ConclusionPucotenlimab plus GP demonstrated promising activity and a manageable safety profile in patients with mTNBC in the first-line setting.

Comparison Efficacy and Safety of Gemcitabine plus Cisplatin and 5-Fluorouracil plus Cisplatin for Metastatic Nasopharyngeal Carcinoma: A Meta-Analysis and Systematic Review.

Objective To compare the efficacy and safety of gemcitabine plus cisplatin (GP) and 5-fluorouracil plus cisplatin (PF) for metastatic nasopharyngeal carcinoma. Methods The clinical trials of GP and PF in the treatment of metastatic nasopharyngeal carcinoma (NPC) were searched in PubMed, EMBASE, Cochrane Library, and Web of Science. The literature search met the inclusion and exclusion criteria. The software Revman 5.4 was used for data analysis, and STATA 15.0 was used for publication bias. Results 10 studies were included in this meta-analysis. The results showed that the GP group had a higher clinical remission rate than the PF group (RR = 1.22, 95% CI (1.03–1.44), P=0.02, P=0.02). GP and PF groups in OS, PFS, and DMFS had the same effect at 1, 2, and 3 years (OS at 1 year: RR = 1.04, 95% CI (0.95–1.15), P=0.37, P=0.37; 2 years: RR = 1.08, 95% CI (0.94 1.23), P=0.28, P=0.28; 3 years: RR = 1.07, 95% CI (0.89 1.29), P=0.46; PFS at 1 year: RR = 1.98, 95% CI (0.29 13.44), P=0.49; 2 years: RR = 3.09, 95% CI (0.10 97.55), P=0.52; 3 years: RR = 0.95, 95% CI (0.73 1.24), P=0.71; DMFS at 1 year: RR = 1.01, 95% CI (0.90–1.14), P=0.83; 3 years: RR = 1.10, 95% CI (0.85–1.41), P=0.47. The number of hematological adverse reactions occurred in GP group was higher than the PF group. Conclusion The GP and PF groups had similar OS, PFS, and DMFS, but the GP group had a higher clinical remission rate. Therefore, GP may be the first choice for metastatic NPC.

P11-2 A case of combined hepatocellular-cholangiocarcinoma successfully treated with atezolizumab plus bevacizumab

A man in his 80‘s with past hepatitis B virus infection and postoperative lung adenocarcinoma at his 70‘s, was diagnosed with intrahepatic cholangiocarcinoma (ICC) and underwent laparoscopic extended right posterior segmentectomy. Histopathological examination revealed StageIIIA combined hepatocellular-cholangiocarcinoma (cHCC-CC) with sarcomatous change (pT3N0M0). Gemcitabine plus cisplatin (GC) therapy was administered as a postoperative adjuvant therapy with reference to the chemotherapy for intrahepatic cholangiocarcinoma.

Neoadjuvant chemotherapy plus tislelizumab followed by concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A single-arm, phase II trial.

6068 Background: Neoadjuvant treatment with gemcitabine plus cisplatin (GP) prior to concurrent chemoradiotherapy (CCRT) has favorable survival outcomes with acceptable toxicity in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC), 10% of whom achieved complete response (CR) after neoadjuvant treatment. Immune checkpoint blockade therapy plus GP regimen has been shown to improve the survival in recurrent or metastatic NPC. We investigated the efficacy and safety of neoadjuvant treatment with GP plus tislelizumab, an anti-PD-1 monoclonal antibody, in previously untreated LANPC. Methods: In this phase II, single-armed Simon two-stage study, eligible patients are of age 18-70, with adequate haematological, renal, and hepatic function, diagnosed with staged III-IVa（AJCC 8th） non-keratinizing LANPC. Enrolled patients received intravenous gemcitabine (1000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and tislelizumab (200mg) on day 1 every 3 weeks for 3 cycles followed by standard CCRT. The primary endpoint was CR rate after neoadjuvant treatment, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator. The secondary endpoints included pathology complete response (pCR) rate, 2-year progress-free survival (PFS), overall survival (OS), locoregional failure-free survival (LRRFS), distant metastasis-free survival (DMFS), and toxicity. This study is registered with ClinicalTrials.gov, NCT04833257, all enrolled patients have finished their treatment and the follow-up is ongoing. Results: From April 14th 2021 to August 5th, 2021, a total of 63 patients (median age 46y, 74.6% male) were enrolled at Sun Yat-sen University Cancer Center. As of January 31st, 2022, the median follow-up is 7.37 months, no patients had disease progression. The CR rate after neoadjuvant treatment was 41.3% (95% CI, 28.8% to 53.8%). The ORR and pCR rate were 88.9% (95% CI, 80.9% to 96.9%) and 75.8% (95% CI, 64.8% to 86.8%), respectively. The incidence of acute treatment-related AEs (trAEs) and immune-related adverse events (irAEs) of grade 3 or 4 was 69.8% and 3.2%, respectively. All of irAEs for grade 3 or 4 were hepatotoxicity and skin rash. Long-term efficacy is awaited. Conclusions: Neoadjuvant treatment with GP plus tislelizumab achieved impressive CR rate and pCR rate with manageable toxicities. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: NCT04833257.

Novel Palliative Chemotherapy for Cholangiocarcinoma

The term cholangiocarcinoma (CC) refers to all tumors arising from bile duct epithelium. CCs are characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. This leads to a paucity of data from which to define the natural history and optimal treatment regimens. Currently, surgical resection remains the only potentially curative treatment, but many patients develop recurrence. In addition, a limited number of patients can be candidates for curative resection at diagnosis. Therefore, chemotherapy is inevitable choice for the treatment of advanced CC. Gemcitabine plus cisplatin (GP) is considered a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed the superiority of gemcitabine plus cisplatin over gemcitabine alone. Treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs. those reported for historical controls treated with gemcitabine-cisplatin alone in a phase II study of 60 patients with locally advanced unresectable or metastatic biliary tract cancer. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. Other active regimens, that could be considered in patients who include have disease progression while receiving GP and who retain an adequate performance status, includes capecitabine plus cisplatin, liposomal irinotecan plus leucovorin-modulated fluorouracil and a fluoropyrimidine alone. We herein review recent published data regarding the use of palliative chemotherapies in CC patients, with a particular focus on novel cytotoxic agents.

Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

Endobiliary Radiofrequency Ablation Combined with Gemcitabine and Cisplatin in Patients with Unresectable Extrahepatic Cholangiocarcinoma.

Background: Endobiliary radiofrequency ablation (RFA) is a promising treatment modality for patients with extrahepatic cholangiocarcinoma (eCCA). However, no study has investigated the combined use of endobiliary RFA and gemcitabine plus cisplatin (GC) chemotherapy. This study aimed to examine the feasibility and efficacy of endobiliary RFA with GC therapy for patients with unresectable eCCA. Methods: The study outcomes included overall survival (OS), progression-free survival (PFS), time to recurrent biliary obstruction (RBO), and adverse events associated with the treatment. These parameters were retrospectively compared between 25 patients who underwent RFA with self-expandable metal stent (SEMS) placement followed by GC therapy (with-RFA group) and a control cohort of 25 patients who underwent SEMS placement alone and GC therapy (without-RFA group). Results: The median time to RBO was significantly longer in the with-RFA group (10.7 versus 5.2 months, p = 0.048). The median OS was significantly higher in patients with locally advanced tumors in the with-RFA group (23.1 versus 16.6 months, p = 0.032), but did not differ significantly in patients with metastasis (11.4 versus 8.5 months, p = 0.180). Similarly, the median PFS was significantly higher in the with-RFA group in patients with locally advanced disease (10.1 versus 7.3 months, p = 0.015), while there was no significant difference in patients with metastasis (5.4 versus 4.4 months, p = 0.529). The rates of various toxicities did not differ significantly between the groups. Conclusions: Endobiliary RFA prolonged the patency period of uncovered SEMS combined with GC therapy in patients with eCCA. Although RFA also yielded survival benefits, its effect was restricted to locally advanced tumors.

Gemcitabine Versus Docetaxel Plus Cisplatin as Induction Chemotherapy in Nasopharyngeal Carcinoma.

To compare tumor volume reduction after induction chemotherapy (IC) with gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin (DP) and to evaluate the influence on subsequent radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). Retrospective clinical study. Patients who received GP or DP IC followed by concurrent chemoradiotherapy (CCRT) were retrospectively enrolled. Propensity score matching (PSM) was adopted to control the balance between the GP and DP groups. A total of 41 patients treated with GP and 53 patients treated with DP were enrolled. After matching, 33 sub-pairs of 66 patients were generated in the post-PSM cohort. As compared with DP, GP was superior in its gross tumor volume of the nasopharynx (GTVnx) reduction (28.88% vs. 18.73%; P=.014) but equivalent in its gross tumor volume of the lymph nodes (GTVnd) reduction (37.58% vs. 29.79%; P=.229). Univariate and multivariate analyses confirmed that the chemotherapy regimen was an independent factor associated with the reduction in GTVnx (P=.011). The GP group exhibited advantages in the dosimetric parameters of the planning target volume of high-risk volume and low-risk volume (PTV1 and PTV2), lenses, temporal lobes, and parotid glands. Univariate and multivariate analyses confirmed that chemotherapy regimen was an independent factor associated with the dosimetric parameters of PTV1, PTV2, lenses, temporal lobes, and parotid glands. GP regimen achieves a greater GTVnx reduction than DP regimen and has an advantage in the dosimetry of subsequent CCRT. 3 Laryngoscope, 132:2379-2387, 2022.

Systematic literature review (SLR) and network meta-analysis (NMA) of first-line therapies (1L) for locally advanced/metastatic urothelial carcinoma (la/mUC).

570 Background: Standard of care (SOC) for 1L la/mUC is gemcitabine plus cisplatin (GC) or carboplatin (GCa), but the landscape is evolving with new therapies emerging. To compare outcomes of other approved/investigational 1L regimens with SOC in the context of recently published data on newer therapies, we updated a previously reported SLR/NMA of phase 2/3 randomized control trials. Methods: The SLR was conducted in line with PRISMA and NICE guidelines (01/2000-05/2020; updated 06/2020-06/2021). Three networks were formed: cisplatin (cis)-eligible/mixed eligibility; cis-ineligible (strict; studies including cis-ineligible patients only); and cis-ineligible (wide; expanded to also include study arms with an investigator’s choice of carboplatin in KEYNOTE-361, IMvigor130, and DANUBE). Comparative efficacy and safety were assessed under a Bayesian framework. Overall survival (OS) and progression-free survival (PFS) with 1L la/mUC regimens vs SOC (GC/GCa) are reported. Results: Among 2,312 citations identified, 55 unique trials were selected for data extraction. Of these, the NMA included 11 studies in the cis-eligible/mixed, 6 in the cis-ineligible (strict), and 8 in the cis-ineligible (wide) network. The NMA excluded therapies that were not effective or adopted in clinical practice; 6 maintenance trials were excluded due to differences in design precluding comparisons. Median OS in the SOC arms was 13.2 mo (95% confidence interval [CI] 12.4-14.0) for cis-eligible/mixed, 9.7 mo (95% CI 6.7-12.8) for cis-ineligible (strict), and 12.0 mo (95% CI 10.4-13.5) for cis-ineligible (wide); median PFS was 6.6 mo (95% CI 6.3-6.9) for cis-eligible/mixed and 5.6 mo (95% CI 5.0-6.3) for both cis-ineligible strict and wide. OS and PFS were similar to SOC across therapies in each network: hazard ratios (HR) ranged 0.7-1.4 for OS for cis-eligible/mixed, 0.9-1.4 for cis-ineligible (strict), and 0.8-1.4 for cis-ineligible (wide) (Table); HR for PFS ranged 0.5-1.6 for cis-eligible/mixed and 0.8-1.1 for both cis-ineligible strict and wide networks; all credible intervals (CrI) crossed or were close to 1. Conclusions: In this updated SLR/NMA, survival outcomes were similar and remained poor among established and emerging 1L la/mUC therapies, despite inclusion of recent trial data. This further highlights the unmet need in this population.[Table: see text]

The influence of major hepatectomy on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subset analysis of JCOG1113.

419 Background: JCOG1113 (UMIN000001685) is a randomized phase III trial in patients (pts) with advanced biliary tract cancers (BTCs) that shows the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) regarding overall survival (OS). Previous reports suggest that a history of major hepatectomy (MH) may affect dose intensity and adverse event (AE) frequency and reduce treatment efficacy in chemotherapy due to impairment of liver function and drug metabolism. We thus investigated whether a history of MH affects the frequency of AEs and treatment efficacy in recurrent BTC pts in JCOG1113. Methods: Among the 354 pts enrolled in JCOG1113, 76 recurrent pts with recurrence after surgery were included in this analysis. We compared the frequency of AEs, progression-free survival (PFS), and OS of GC vs. GS in pts treated with MH vs. non-major hepatectomy (NMH). Results: Of the 76 pts, 17 on GC and 13 on GS were included in the MH group, while 20 on GC and 26 on GS were included in the NMH group. The primary sites were only intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma in the MH group, and there were no differences between the groups regarding sex, performance status, biliary drainage, or site of recurrence. The hazard ratio (HR) of GS to GC for PFS was 0.74 (95% CI 0.35–1.56) in the MH group and 0.97 (95% CI 0.52–1.82) in the NMH group. The hazard ratio (HR) of GS to GC for OS was 0.99 (95% CI 0.418–2.36) in the MH group and 1.17 (95% CI 0.59–2.33) in the NMH group. The median PFS and OS for GS in the MH group were 12.2 months and 21.5 months. These were longer than the 6.8 months and 15.1 months in the original results for GS in JCOG1113. Regarding AEs, Grade 3-4 AEs, specifically neutrophil count decreased (73.1%/92.3%), platelet count decreased (3.9%/15.4%), and rash (7.7%/15.4%), were more common in MH pts than NMH pts on GS. On GC, AEs in the MH and NMH pts did not show any consistent trends. The relative dose intensities (RDIs) of gemcitabine (70.7%/62.5%) and S-1 (70.4%/54.5%) were lower in MH pts than NMH pts on GS. The RDIs of gemcitabine (67.4%/63.0%) and cisplatin (73.6%/65.0%) were slightly lower in MH pts than NMH pts on GC. Conclusions: For pts with a history of MH, some AEs increased, and the RDIs were lower, especially that of S-1 for GS. On the other hand, the HR for PFS suggests that GS may be more effective than GC in MH pts.

The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: an exploratory analysis of JCOG1113

In the FUGA-BT trial (JCOG1113), gemcitabine plus S-1 (GS) showed non-inferiority to gemcitabine plus cisplatin (GC) in overall survival (OS) with good tolerance for patients with advanced biliary tract cancer (BTC). We performed a subgroup analysis focused on the elderly cohort of this trial. All 354 enrolled patients in JCOG1113 were classify into two groups; < 75 (non-elderly) and ≥ 75 years (elderly) group. We investigated the influence of age on the safety analysis, including the incidence of chemotherapeutic adverse events and the efficacy analysis, including OS. There were no remarkable differences in OS between the elderly (n = 60) and the non-elderly groups (n = 294). In the elderly group, median OS was 12.7 and 17.7 months for those who received GC (n = 20) and GS (n = 40), respectively. The prevalence of all-grade adverse events was similar between the elderly and the non-elderly groups. However, among the elderly group, Grade ≥ 3 hematological adverse events were more frequently observed in the GC arm than in the GS arm. The clinical outcomes of combination chemotherapy in elderly patients with advanced BTC were comparable to non-elderly patients. GS may be the more favorable treatment for elderly patients with advanced BTC.

Comparative efficacy of 10 Chinese herbal injections combined with GP regimen chemotherapy for patients with advanced NSCLC a systematic review and network meta-analysis.

Background: Numerous studies have indicated that some Chinese herbal injections (CHIs) might have a beneficial treatment effect when used in combination with chemotherapy. However, the results of these studies have been inconsistent. The aim of this network meta-analysis (NMA) was to evaluate and compare the clinical efficacy and safety of different CHIs combined with gemcitabine plus cisplatin (GP) regimen chemotherapy with that of GP regimen chemotherapy alone in the treatment of patients with advanced non-small cell lung cancer (NSCLC).Materials and Methods: Eight databases were systematically searched to identify randomized clinical trials (RCTs) from the date of inception of the database to August 11, 2021. The primary outcome measures were the objective response rate (ORR) and adverse reactions (including nausea and vomiting, and leukopenia). The secondary outcome measures were median survival time (MST) and quality of life (QOL). The quality of the included studies was assessed using the Cochrane risk of bias tool. Standard pair-wise and Bayesian NMAs were carried out to compare the effectiveness and safety of different CHIs combined with GP regimen chemotherapy using WinBUGS 14 and Stata 15.1 software. Sensitivity analysis and Egger's test were also performed to check robust.Results: A total of 92 eligible RCTs involving 7,728 patients and 10 CHIs were included. The results showed that Kangai injection (KAI), Kanglaite injection (KLT), Aidi injection and Compound Kushen (CKSI) injection displayed obvious advantages in both efficacy and safety. Aidi+GP (79.0%) showed great advantages of ORR, and KAI+GP and KLT+GP had the lowest probability in terms of leukopenia (4.4%) and nausea and vomiting (24.2%). Besides, KLT+GP was shown to positively affect MST. According to the subgroup analyses, CHIs might have a limited effect in reducing adverse reactions, and have a similar effect in squamous cell carcinoma and adenocarcinoma.Conclusions: KAI+GP of adjuvant drugs, Aidi+GP and CKSI+GP of anticancer drugs appeared to be the advantageous treatment options for patients with advanced NSCLC, owing to its superior therapeutic performance and reduced adverse reactions. KLT+GP might prolong survival. Nevertheless, additional results from multicenter trials and high-quality studies will be pivotal in supporting our findings.

The best choice of induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma: Bayesian network meta-analysis.

The determination of the optimal induction chemotherapy (IC) regimen for patients with locally advanced nasopharyngeal carcinoma (NPC) remains controversial. Eligible trials included in this Bayesian network meta-analysis were judged by synthetically evaluating survival and safety outcomes. The analysis revealed that the combined IC regimen of gemcitabine plus cisplatin (GP) gained not only the most favorable overall survival (OS) benefit but also longer distant metastasis-free survival and manageable adverse events (AEs). Additionally, combination IC regimen of mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin had insufficient significant efficacy on complete response. Docetaxel combined with cisplatin and fluorouracil induction regimen provided the first exact probability of efficacy in term of local recurrence-free survival, ranking second in OS, but accompanied by the highest rates of grade 3 or above AEs. GP regimen appears to be currently the best choice of IC regimen for combined benefit of patients with locally advanced NPC.