Chemotherapy In First-line Treatment Research Articles

BTK INHIBITORS IN CNSL AND HIGH‐RISK/REFRACTORY DLBCL PATIENTS: A REAL‐WORLD STUDY

Objective: The effectiveness and prognosis of a BTki-containing regimen in first-line treatment and relapsed/refractory patients were assessed in this study. Methods: There were 26 patients with DLBCL. BTKi was administered to patients with newly diagnosed, relapsed, refractory primary PCNSL and high-risk/refractory systemic DLBCL, and the effectiveness and PFS were evaluated. Results: The BTKi therapy study included 26 participants (16 PCNSL, 10 DLBCL). Among PCNSL,3 patients who had achieved PR following MTX-based first-line chemotherapy were given BTKi as a monotherapy for disease recurrence. BTKi patients lived for an average of 5 (1–8) months before dying from disease progression, which is 5 months longer than the typical patient survival period following chemotherapy recurrence. After three rounds of MTX-based chemotherapy, none of the six patients with refractory PCNSL achieved PR. After BTKi was utilized as second-line therapy, the average survival time was increased by 12 (2–21) months. Three patients received early treatment, while the remaining three received BTKi after the third round of medicine. Early patients had a longer average survival period than late ones (11 months vs. 10 months). The remaining seven high-risk patients received first-line chemotherapy and BTKi treatment. The median follow-up duration was 5 months, the ORR was 100%, and neither the median PFS nor the median OS were achieved. The mean maintenance time was 8 months. Among 10 patients with DLBCL, 8 of them are high risk group, and 2 had refractory disease. When the disease of two SCNSL patients advanced, BTKi was used in conjunction with chemotherapy as a salvage treatment, and BTKi was kept up for an average of 5 months. The efficacy was evaluated as PD. The ORR was 80% (4/5, 1 case was not assessed) and CR rate was 100% in high risk group. Four of these CNS-IPI high-risk DLBCL patients had adrenal involvement and a high IPI score, with BTKi maintained for an average of 6 months, two of them achieved CR, one of PD, and 1 case was not evaluated. The efficacy evaluation was CR in the other two high-risk CD5+ patients, whose BTKi was sustained for 12 months and 6 months, respectively. After receiving standard chemotherapy, the remaining 2 refractory patients kept getting worse. One patient with hepatitis B cirrhosis had elevated AST and ALT levels after one course of medication, so BTKi was stopped. The other patient was kept on BTKi alone for 4 months, but the efficacy was still PD. Patients with PCNSL have a dismal prognosis, in particular, the average survival time for R/R patients is less than two months. The research was funded by: National Natural Science Foundation of China (8226010026), Natural Science Foundation of Gansu Province (22JR11RA053) Keywords: aggressive B-cell non-Hodgkin lymphoma, molecular targeted therapies, combination therapies No conflicts of interests pertinent to the abstract.

Psycho-emotional well-being of non-hodgkin lymphoma patients

The given study focuses on the evaluation of the psycho-emotional well-being of patients with non-Hodgkin’s lymphomas (NHL) according to age, gender, living environment, morphological subtype, stage, primary tumor focus, Charlson comorbiditiesindex, and completion of first-line chemotherapy treatment. To carry out the study, a number of 126 patients aged between 18 and 78 years, included in the treatment and monitored in the Department of Hematology, IMSP Oncological Institute, during the years 2020-2022, were selected. The Global Well Being (GWB) score was used to test the proposed hypotheses. The results illustrate statistically significant correlations between GWB score and gender, living environment, extranodal onset, and treatment period. The lack of statistically significant correlations was appreciated between the GWB score and age, disease stage, comorbidities.

Cost-Effectiveness Analysis of Monoclonal Antibodies Associated With Chemotherapy in First-Line Treatment of Metastatic Colorectal Cancer

ObjectivesThis study aimed to evaluate the cost-effectiveness of anti–epidermal growth factor receptor (cetuximab and panitumumab) or anti–vascular endothelial growth factor (bevacizumab) monoclonal antibodies associated with conventional chemotherapy (CT) (fluorouracil and leucovorin with irinotecan) as a first-line treatment for unresectable metastatic colorectal cancer. MethodsA partitioned survival analysis model was adopted to simulate direct health costs and benefits comparing therapeutic options in a 10 years’ time horizon. Model data were extracted from the literature and costs were obtained from Brazilian official government databases. The analysis considered the perspective of the Brazilian Public Health System; costs were measured in local currency (BRL) and benefits in quality-adjusted life-years (QALY). A 5% discount rate was applied to costs and benefits. Alternative willingness-to-pay scenarios, varying from 3 to 5 times the cost-effectiveness threshold established in Brazil, were estimated. The results were presented incremental cost-effectiveness ratio (ICER), and both deterministic and probabilistic sensitivity analyses were performed. ResultsThe most cost-effective choice would be the association of CT with panitumumab, with an ICER of $58 330.15/QALY compared with isolated CT. The second-best option was CT with bevacizumab and panitumumab, with an ICER of $71 195.40/QALY compared with panitumumab alone. Although having higher costs, the second-best option was the most effective. Both strategies were cost-effective in part of the Monte Carlo iterations, considering the 3× threshold. ConclusionsThe therapeutic option CT + panitumumab + bevacizumab represents the most significant effectiveness gain in our study. It is the second-lowest cost-effectiveness, and this option includes monoclonal antibodies association for patients with and without KRAS mutation.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Real-world retrospective review of monotherapy following platinum-based chemotherapy for metastatic urothelial cancer

To compare estimated survival times of patients who had received maintenance monotherapy with gemcitabine (GEM), or an immuno-oncology (IO) drug (i.e., pembrolizumab or avelumab) or both therapies (one after the other) following platinum-based combination chemotherapy for metastatic urothelial carcinoma (UC) in a real-world setting. For this retrospective study, we included consecutive patients with metastatic UC who had received first-line platinum-based chemotherapy followed by second-line treatment at our centre from March 2008 to June 2020. Of the 74 patients identified, 58 had received monotherapy as second line treatment, and 16 had received combination chemotherapy (i.e., non-monotherapy). The estimated median duration of survival was significantly longer in the monotherapy group compared with the non-monotherapy group (29 vs 7 months). Multivariate analysis showed that the outcome of the first-line chemotherapy treatment was the most important prognostic factor for survival. There was no significant difference in survival times between monotherapy with GEM or IO drugs. In addition, survival was significantly prolonged when GEM therapy was administered following IO drugs compared with GEM therapy alone. Monotherapy following primary chemotherapy for advanced UC significantly prolonged survival times, and IO drug therapy remained effective when followed by GEM single agent maintenance therapy.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Sex and gender differences in treatment intention, quality of life and performance status in the first 100 patients with periampullary cancer enrolled in the CHAMP study

BackgroundPeriampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3rd leading cause of cancer death for both sexes and while surgery is the only option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial.MethodsThe study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan–Meier analysis.ResultsThere was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline.ConclusionsThis study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes.Trial registrationNCT03724994.

Expression levels of Ki-67 and cyclin D1 in advanced nasopharyngeal carcinoma and its prognosis

Introduction and Aim: Nasopharyngeal cancer (NPC) prognosis has been associated with cyclin D1 and Ki-67. These tumor markers had never been tested in NPC patients in Indonesia before. Therefore, this study aims to evaluate the relationships between Ki-67 and cyclin D1 expression levels and the clinicopathological features of nasopharyngeal cancer (NPC) patients. Materials and Methods: During the years 2015 until 2018, thirty-one nasopharyngeal cancer patients were studied in a cohort study at RSUPN Dr. Cipto Mangunkusumo. Patients aged 18 years, diagnosed with NPC according to the histopathological results, metastasis NPC, Eastern Cooperative Oncology Group 0–1, and those who had completed first-line chemotherapy treatment with 5–fluorouracil were included in this study. The Ki-67 and cyclin D1 expression levels were evaluated with the h-score. The NLR values were collected prior to the treatment. The 2-year survival rate was analyzed based on the optimal cut-off value obtained. The optimal cut-off values of Ki-67 and cyclin D1 were categorized into high- and low-expression groups to observe the 2-year mortality. Results: The relationships between Ki-67 and cyclin D1, clinical, pathological, and prognosis of patients were examined. Patients with Ki-67 high expression had a worse 2-year survival rate than those with low expression (p0.05). Ki-67 expression was found to be significantly related to adverse outcomes (p0.05, OR: 41.107, 95% CI: 2.600–649.940), while the cyclin D1 expression was not significantly related to adverse outcomes (p0.05). Conclusion: Ki-67 expression was associated with poor prognosis in NPC patients. Nevertheless, further research is required to explore the specific mechanism of cyclin D1 expression in NPC prognosis.

Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.

477 Background: First-line therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemo-immunotherapy trials failed to show a clear benefit over chemotherapy alone. We sought to use real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy or combination chemo-immunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). Methods: We used the National Cancer Database to identify patients with stage IV UCB diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt. An extension of inverse probability treatment weighting (IPTW) obtained from multinomial logistic regression was used to balance clinical and sociodemographic differences between treatment groups. Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. Results: A total of 4,169 patients were identified in the cohort; 3,255 (78.1%) were treated with chemotherapy, 601 (14.4%) with immunotherapy, and 313 (7.5%) with combination treatment. Multivariable analysis identified increasing age (RRR: 1.07, 95% CI, 1.06-1.08), comorbidity burden (Charlson-Deyo 2, RRR: 1.65, 95% CI, 1.21-2.24 and Charlson-Deyo 3, RRR: 2.11; 95% CI, 1.51-2.93), and treatment at an academic facility (RRR: 1.26; 95% CI, 1.03-1.53) as independent predictors of receiving immunotherapy. Treatment at an academic facility (RRR: 1.29, 95% CI, 1.01-1.65) was associated with receipt of combination treatment. After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95% CI, 0.62-0.83), but not immunotherapy alone, was associated with improved survival compared to chemotherapy. These data are limited by inability to determine platinum eligibility, and residual confounding. Conclusions: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Modest real-world utilization of chemo-immunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy. The study is limited by retrospective design; prospective data are necessary to identify patients who may benefit from combination chemo-immunotherapy.

Photodynamic therapy in combination with immune checkpoint inhibitors plus chemotherapy for first-line treatment in advanced or metastatic gastric or gastroesophageal junction cancer: A phase 2-3 clinical trial protocol.

Introduction: The immune checkpoint inhibitor (ICI) has been approved as the first-line therapy for metastatic gastric cancer in China. The treatment response of immune checkpoint inhibitor is highly dependent on the immune condition within the tumor microenvironment. Photodynamic therapy (PDT) has a long history in cancer treatment, and recent studies showed it had an immunomodulatory effect on the tumor. Here we will conduct a trial to assess whether or not a combination with Photodynamic therapy will improve the outcomes of immune checkpoint inhibitor-based treatment in patients with advanced or metastatic gastric cancer. Methods: This study is a single-center, open-label, randomized controlled, phase 2-3 trial. Patients (18-65years old) with untreated gastric or gastroesophageal junction adenocarcinoma will be eligible for this trial. Sixty participants will be enrolled and randomly divided into the test group (n = 30) and control group (n = 30) to receive photodynamic therapy in combination with immune checkpoint inhibitor plus chemotherapy and immune checkpoint inhibitor plus chemotherapy, respectively. The primary is progression-free survival (PFS). The secondary outcomes include objective response rates (ORRs) and the occurrence of adverse events. In addition, we will also assess the changes in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment after photodynamic therapy treatment in the test group. Evaluation of the tumor response will be performed every two cycles for a maximum of eight cycles. Discussion: Photodynamic therapy has an immunomodulatory effect on the tumor microenvironment; however, this has not been demonstrated for gastric cancer in a clinical trial. Based on our experience of photodynamic therapy treatment in digestive tract tumors, we plan to conduct a randomized controlled trial on this topic. This will be the first study to evaluate the synergistic effect of photodynamic therapy with immunochemotherapy for patients with advanced gastric cancer. Ethics and dissemination: It was approved by the Institutional Research Ethics Committee of Lanzhou University Second Hospital (No. 2022A-491). When this trial is completed, it will be shared at conferences and submitted for a potential publication in a peer-reviewed journal. Clinical Trial Registration: http://www.chictr.org.cn/, identifier ChiCTR2200064280.

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma.

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9nm with a zeta potential of +22.3mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10-80μg/ml), and MTT cytotoxic assay (concentration range of 10-90μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

The maximum tumor growth rate predicts clinical outcomes of patients with small-cell lung cancer undergoing first-line chemotherapy plus immune-checkpoint inhibitor therapy.

Currently, no biomarkers can accurately predict survival outcomes in patients with SCLC undergoing treatment. Tumor growth rate (TGR; percent size change per month [%/m]) is suggested as an imaging predictor of response to anti-cancer treatment. We aimed to evaluate the predictive role of the maximum TGR (TGRmax) for outcomes of small-cell lung cancer (SCLC) patients undergoing first-line chemotherapy plus immune-checkpoint inhibitor (ICI) treatment. Patients with SCLC receiving first-line chemotherapy plus immunotherapy were analyzed within this retrospective study. The X-tile program was used to identify the cut-off value of TGRmax based on maximum progression-free survival (PFS) stratification. The Kaplan-Meier methods and Cox regression models were used to evaluate the effect of the presence of TGRmax on PFS and overall survival (OS). In total, 104 patients were evaluated. Median (range) TGRmax was -33.9 (-65.2 to 21.6) %/m and the optimal cut-off value of TGRmax was -34.3%/m. Multivariate Cox regression analysis revealed that patients with TGRmax > -34.3%/m was associated with shorter PFS (hazard ratio [HR], 2.81; 95% CI, 1.71-4.63; p < 0.001) and OS (HR, 3.17; 95% CI, 1.41-7.08; p=0.005). In patients who received partial response (PR), Kaplan-Meier survival analyses showed that superior PFS and OS (p=0.005 and p=0.009, respectively) benefit was observed when TGRmax ≤-34.3%/m. SCLC patients with TGRmax > -34.3%/m had worse PFS and OS in first-line ICI plus platin-based chemotherapy. TGRmax could independently serve as an early biomarker to predict the benefit from chemoimmunotherapy.

COVID-19 infection during treatment with pembrolizumab in combination with chemotherapy for the treatment of lung adenocarcinoma

The use of pembrolizumab with chemotherapy in first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) is an opportunity for patients to suppress their disease and increase their chances of life extension. COVID-19 (Coronavirus Disease 2019) vaccination is an opportunity for cancer patients to reduce their risk of disease and have a benign disease course. In this report, we present a benign course of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2 ) infection in 68-year-old patient with metastatic lung adenocarcinoma undergoing chemoimmunotherapy who had previously received full COVID-19 vaccination. The control CT scans performed after 3 months of treatment showed partial regression of the tumor mass. On control tomography after 6 months, an intensification of fibro-consolidative changes and ground glass opacities were described. The lesions were characteristic of a history of SARS-CoV-2 infection. The neoplastic lesions described on tomography showed stabilization. After 9 months, long-term stabilization of the disease was achieved. Patients undergoing immunotherapy or chemoimmunotherapy may be at risk of developing severe COVID-19. Therefore, vaccination against SARS-CoV-2 should be strongly recommended in lung cancer patients undergoing immunotherapy.

Economic evaluation of first-line sugemalimab plus chemotherapy for metastatic non-small cell lung cancer in China.

To evaluate the economics of sugemalimab plus chemotherapy in the first-line treatment of metastatic non-small cell lung cancer, and to provide a reference for the formulation of relevant medical insurance policies and rational drug use. From the perspective of the Chinese health system, a three-state partitioned survival model was constructed based on data from a phase III randomized clinical trial (GEMSTONE 302) to evaluate the cost-utility of sugemalimab plus chemotherapy compared with chemotherapy in first-line treatment of metastatic non-small cell lung cancer. Model results were expressed as total cost, life years, quality-adjusted life years, and incremental cost-effectiveness ratio. The robustness of the underlying analysis results was verified using one-way sensitivity analysis and probabilistic sensitivity analysis. The results of the base-case analysis showed that sugemalimab plus chemotherapy yielded 1.63 QALYs at a total cost of 130,667.70 USD, chemotherapy yielded 1.04 QALYs at a total cost of 64,001.02 USD, and the ICER was 113,155.52 USD/QALY, which was well above the current willingness-to-pay threshold in China (3 times 2021 per capita GDP) (36,203.88 USD). This study suggests that sugemalimab in combination with a chemotherapy regimen is more effective but not economical for patients with metastatic non-small cell lung cancer receiving first-line therapy in China and that a reasonable reduction in drug prices could improve the probability of it being economical.

Blinatumomab As Toxicity Sparing First Line Treatment of Children and Young Persons with B-Precursor Acute Lymphoblastic Leukaemia (B-ALL)

Introduction Recent studies have demonstrated that Blinatumomab is more effective and less toxic than intensive chemotherapy in children and young persons (CYP) with relapsed B-ALL. Although Blinatumomab is standard of care in adults with persistent MRD during first line therapy based on the BLAST study, there is no published evidence in CYP of its efficacy and toxicity in this setting. We report our experience of Blinatumomab as a toxicity sparing alternative to chemotherapy in first line treatment of CYP with B-ALL. Patients and Methods We audited the outcome of patients treated according to a consensus UK guideline for first line treatment with Blinatumomab of CYP patients with B-ALL who were considered unfit for post-remission intensive chemotherapy or CR1 HSCT because of toxicity to previous chemotherapy or significant co-morbidities. Treating clinicians obtained consent for treatment with Blinatumomab as standard of care after counselling patients and carers about the risk and benefits of this approach. The guideline mandated discussion of all such patients at national tumour board meetings and data was captured through a referral proforma and follow-up questionnaire. It recommended replacing consolidation and/or interim maintenance phases with 2 cycles of blinatumomab as a single agent with a 1-2 week break between cycles. Patients who obtained an MRD response (defined as MRD <0.01%) received delayed intensification (DI) followed by maintenance, or maintenance therapy alone if they were unfit for DI. Patients who had persistent MRD >0.01% were categorised as Blinatumomab failures and received either further chemotherapy, HSCT or CART depending on performance status. Events were defined as death, relapse, or secondary cancer. Results Sixty patients were eligible for analysis, including 4 cases of Ph+ ALL and 8 with Down syndrome. Compared to the B-ALL cohort in a previous trial, UKALL 2003, there was a higher proportion of NCI high risk, cytogenetic high risk, end of induction MRD positive and Down Syndrome patients (Table 1). All patients were in morphological complete remission prior to receiving Blinatumomab. Blinatumomab was administered for toxicity (47/60 (78%), including G3/4 pancreatitis, typhlitis, severe infections often requiring intensive care or surgery, disseminated fungal infections, CNS haemorrhage or liver failure) or co-morbidities (Down syndrome, Li-Fraumeni syndrome (n=2), Schimke immune-osseous dysplasia and 7q11.21-23 duplication) or in one case to minimise transfusion requirements (Jehovah's witness.) In the remaining 13 cases, blinatumomab was either administered for end of consolidation MRD of ≥0.05% (n=10) in patients unfit for intensive chemotherapy/HSCT, or positive end of induction MRD in patients with HR cytogenetics (n=3). Blinatumomab replaced consolidation and interim maintenance therapy in 32/60 (53%) cases, and interim maintenance in the remaining 28/60 (47%) cases. Blinatumomab was well tolerated with 1 G3 neurotoxicity (seizure in a Down syndrome patient who had not received prophylactic anti-convulsants) and no grade 2-4 CRS. Of the 50/60 patients with positive MRD pre-Blinatumomab (median = 0.1%, range = 0.01%-8%), 48 (96%) had a reduction in level to <0.01% (45 after cycle 1, 3 after cycle 2), and 10 patients maintained MRD negativity before and after 2 cycles of Blinatumomab. In the two patients who did not respond (3%), 1 received CART followed by transplant for persistent MRD, the other is receiving intensive chemotherapy. Of the responders, 47 (80%) received DI and maintenance and 10 maintenance alone. With a median follow up of 16 months (range 2-44 months), 2 patients have relapsed (1 at 2 years, the other at 9 months) but remain alive. The 4 patients with Ph+ ALL and the 8 with Down syndrome are alive and in remission, with a median follow up of 12.5 months (range 7-22 months). Conclusion In this large case series, we found Blinatumomab is safe and highly active with promising short-term efficacy in a higher risk cohort of CYP patients with B-ALL in first remission. Our results support its use in place of intensive chemotherapy for patients with relative chemo-intolerance. Furthermore, if the efficacy is sustained on longer follow-up, the results argue for replacing parts of post-remission intensive chemotherapy with Blinatumomab to reduce attendant morbidity and mortality. SS and AV are joint senior authors, AH and AM joint first authorsFigure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Case report: The remarkable response of pembrolizumab combined with RC48 in the third-line treatment of metastatic urothelial carcinoma

Systemic chemotherapy has been the mainstay treatment for locally advanced or metastatic urothelial carcinoma (UC). In the past few years, novel immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) have improved the treatment of advanced UC. Here, we report systemic therapy of a 68-year-old male diagnosed with HER2 positive (immunohistochemistry 3+), programmed cell death ligand 1(PD-L1) negative metastatic UC, and renal insufficiency. He had encountered numerous metastases and failed first-line platinum-based chemotherapy and second-line treatment with pembrolizumab and trastuzumab. During third-line treatment with RC48 (a HER2 targeting ADC) combined with pembrolizumab, he achieved a rapid partial response (PR) in the first evaluation and subsequent complete response (CR) on PET/CT and long-term progression-free survival (>12 months) at the last follow-up on 25 August 2022. There are no grade 3 or 4 adverse events or aggravations of renal insufficiency during the third-line therapy. RC48 combined with pembrolizumab demonstrated outstanding efficacy and safety in this HER2-positive metastatic UC patient. ADC combined with ICI is a promising anti-tumor strategy that deserves further exploration in advanced UC.

Survival Outcomes for High Risk Primary Refractory and Relapsed Large B-Cell Lymphoma (LBCL) within the Veterans Health Administration (VHA)

Introduction: Even in the Rituxan era, patients with primary refractory or relapsed LBCL have poor outcomes. The standard of care for these patients is salvage therapy (ST) as second-line treatment followed by high dose therapy with autologous stem cell transplant (ASCT) in chemosensitive patients with an estimated 30-40% of ST responders deemed eligible to undergo transplant (PMID: 28774879). Currently, chimeric antigen receptor (CAR) T-cell therapy is the standard of care for high risk LBCL (high International Prognostic Index (IPI), HIT status) who do not respond to ST and have manageable safety profiles and high efficacy. Promising CAR T data is also emerging for early chemotherapy failure and as alternative second-line therapy (PMID: 35314842). The purpose of this study is to analyze the treatment patterns and survival outcomes of primary refractory and relapsed population of LBCL within the VHA. Methods: This is a retrospective chart review of 5199 randomly selected patients with an ICD code for lymphoma treated within the VHA between 01/01/2011 and 12/31/2019. Data abstractors included patients with LBCL who completed first-line chemotherapy treatment and had documented post-treatment scans (PET, CT). We defined primary refractory as either stable disease (SD) or progressive disease (PD) based on post-treatment scans and relapsed disease as recurrence of disease within 12 months of post treatment scans. Median overall survival (OS) was calculated using the Wilcoxon-Mann-Whitney test. Results: A total of 2288 patients met inclusion criteria who received or completed treatment at the VHA. Baseline characteristics are outlined in Table 1. From our analysis, 299 (13.1%) of patients were primary refractory. Median age was 68.9 years and 97% were male. European Cooperative Oncology Group (ECOG) was 0-2 (81.3%). Stage at diagnosis was III-IV (83.9%). Most patients had an IPI score ≥3 (85%). Germinal center B-Cell (GCB) accounted for 48.2% while Activated B-Cell (ABC) was 24.4%. Gene rearrangement was present in 26% of the patients with available data. Of the 119 (63.9%) patients who received second line treatment, only 19 (6.4%) were able to receive high dose chemotherapy and underwent an ASCT and only 3 (1%) of patients received CAR T-cell therapy. One year and two year overall survival was 47.8% and 24.7% respectively. Median OS for this population was 11.0 months. There were 105 (4.6%) relapsed patients in our cohort. Median age was 64.7 years and 96.2% were male. ECOG was 0-2 (85.7%). Stage at diagnosis was III-IV at 84.8%. Most patients had an IPI score ≥3 (80%). GCB accounted for 37.1% while ABC was 35.2%. Gene rearrangement was present for 20% of the patients with available data. In this group, 16 (15.2%) of patients received high dose chemotherapy and ASCT and only 3 (2.9%) received CAR T-cell therapy. One year and two year overall survival was 72% and 41% respectively. Median OS for this population was 21.3 months. 1403 (61%) of patients had complete response (CR) with a 1 and 2 year survival rate of 97 % and 93 % respectively and median OS of 69.3 months. Conclusion: This is one of largest data sets studying the rate of primary refractory and relapsed LBCL in the VHA and shows that more than two-thirds of these patients have high risk disease. Furthermore, a significant portion of these veterans did not receive second-line therapy including ASCT as compared to previously reported real world and clinical trial data. It is possible that our patient populations had higher rates of chemoresistance, were deemed ineligible for transplant due to age or performance status, or had higher comorbidities. Emerging data on newer antibodies and CAR T-cell therapy for early chemotherapy failure or second-line therapy might be a more appropriate option for our veteran population. In conclusion, CAR T-Cell therapy will likely replace the treatment paradigm for primary refractory or relapsed disease for early treatment failures in patients with LBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

338P Anti PD1 is superior to anti PDL1 when combined with chemotherapy in first-line treatment for metastatic non-small cell lung cancer (mNSCLC): A network meta-analysis

Platinum based chemotherapy (CT) with anti PD1/PDL1 is now a standard first line therapy in the management of mNSCLC without targetable driver mutations. PDL1 is expressed on tumour cells and PD1 is expressed on immune cells and these alternate mechanisms may alter clinical outcomes after tumour cell death. A network meta-analysis (NWM) showed anti PD1 + CT was superior to anti PDL1 + CT in overall survival (OS). However, only one anti PDL1, atezolizumab, was included in the analysis. More recently, several randomised controlled trials (RCT) involving newer anti PD1/PD L1 agents have been reported.

311P Cost-effectiveness of alectinib compared with chemotherapy in first-line treatment for anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer in Thailand

Alectinib demonstrated significantly improved clinical outcomes in patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in a randomized Phase III trial (ALEX). There is no study examining long-term health and economic outcomes of this first-line treatment of ALK+ advanced NSCLC compared with chemotherapy that has been a standard of care in Thailand.

Treatment patterns and outcomes of immunotherapy in extensive-stage small-cell lung cancer based on real-world practice.

The application of immune checkpoint inhibitors (ICIs) represents a breakthrough in the current landscape for the treatment of extensive-stage small-cell lung cancer (ES-SCLC), but the real-world outcome is limited. This study aimed to investigate the treatment options and efficacy evaluation of first-line, second-line, and subsequent-line immunotherapy in routine practice. A retrospective analysis of ES-SCLC patients treated with ICIs was conducted between May 2016 and September 2021. Objective response rate, disease control rate, progression-free survival (PFS) and overall survival were assessed between groups to explore the value of ICIs at different treatment time periods. PFS1 and PFS2 were defined as the duration from initial therapy to disease progression or death in first-line or second-line treatment. Ninety-six patients with ES-SCLC were included. PFS1 was prolonged in patients treated with first-line ICIs-combined therapy (median PFS1 7.20 months vs. 5.30 months, hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.36-087, p=0.0085). For patients who progressed after first-line ICIs treatment (N=22), PFS1 + PFS2 was longer in the second-line ICIs continuation group with no significant difference (median PFS1 + PFS2 11.27 months vs. 7.20 months, HR 0.45, 95% CI 0.14-1.51, p=0.19). For patients who experienced a progression event after first-line chemotherapy (N=50), PFS2 and PFS1 + PFS2 were prolonged in patients who accepted second-line ICIs-combined therapy without significant difference (median PFS2 4.00 months vs. 2.43 months, HR 0.59, 95% CI 0.33-1.05, p=0.070; median PFS1 + PFS2 11.30 months vs. 8.70 months, HR 0.53, 95% CI 0.29-0.98, p=0.056). First-line ICIs plus chemotherapy should be applied in the clinical practice of ES-SCLC. If patients did not receive ICIs plus chemotherapy in first-line treatment, therapies that include ICIs in second-line treatment should be considered.