First-line Treatment In Chinese Patients Research Articles

Cost-Effectiveness of Zanubrutinib Versus Bendamustine and Rituximab in Patients With Untreated Chronic Lymphocytic Leukemia

Zanubrutinib, a potent and specific irreversible Bruton's tyrosine kinase inhibitor, has proven to be effective in untreated chronic lymphocytic leukemia (CLL), whether used alone or in combination with other therapies. Here, we compared the cost-effectiveness of zanubrutinib with bendamustine-rituximab (R-bendamustine) to determine its effectiveness as the first-line treatment for Chinese patients with untreated CLL. The evaluation utilized a partitioned survival model, constructed using TreeAge Pro 2011 software, incorporating data from SEQUOIA trial (NCT03336333). Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. In this analysis, the quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, and lifetime cost were calculated from the Chinese health care system perspective. Sensitivity analyses, including 1-way analysis and probabilistic sensitivity analysis, were carried out to explore the uncertainty of the modeling results. Additionally, several scenario analyses, including different zanubrutinib price calculation and 20-year time horizon, were evaluated. The findings revealed that zanubrutinib had an incremental cost-effectiveness ratio of $58,258.18 per additional QALYs gained compared with bendamustine-rituximab, with zanubrutinib being cost-effective only if its price was reduced by more than 30%. Research indicated that zanubrutinib achieved at least a 3.70% probability of cost-effectiveness at the threshold of $38,223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to the utility of progressed disease. The study highlighted the importance of considering the cost-effectiveness of zanubrutinib at its current price point for patients with untreated CLL in China, emphasizing the need for further assessment and potential pricing adjustments to enhance its economic viability in clinical practice.

394TiP A phase IIIb, single-arm, open-label, multi-center study on durvalumab in combination with gemcitabine-based chemotherapy as first-line treatment for Chinese patients with unresectable biliary tract cancers: TopDouble

394TiP A phase IIIb, single-arm, open-label, multi-center study on durvalumab in combination with gemcitabine-based chemotherapy as first-line treatment for Chinese patients with unresectable biliary tract cancers: TopDouble

Cost-effectiveness of BTK inhibitors vs bendamustine and rituximab in chronic lymphocytic leukemia patients.

Background: We aimed to compare the cost-effectiveness of bruton tyrosine kinase inhibors (BTKis) versus bendamustine-rituximab (R-bendamustine) as a first-line treatment for Chinese patients with relapsed or refractorychronic lymphocytic leukemia. Methods: A partitioned survival model was constructed using TreeAge Pro 2022 software and transition probabilities were estimated from the reported survival probabilities using parametric survival modeling. One-way analysis and probabilistic sensitivity analysis were performed to explore the uncertainty of the modeling results. In addition, several scenario analyses were evaluated. Results: In comparison to R-bendamustine, zanubrutinib had an incremental cost-effectiveness ratio (ICER;life years) and ICER (quality-adjusted life years) of US$12,173.38 and $17,983.40, respectively. While ibrutinib had a higher ICER relative to R-bendamustine. Conclusion: Zanubrutinib was cost-effective for patients with relapsed or refractory chronic lymphocytic leukemia in China.

Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.

Pegylated liposomal doxorubicin and carboplatin versus paclitaxel and carboplatin as first-line treatment for Chinese patients with ovarian cancer: A multi-center, randomized, open-label trial.

5556 Background: Paclitaxel combined with carboplatin is a standard first-line chemotherapy regimen for ovarian cancer. This study was designed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) plus carboplatin (CD) compared with paclitaxel plus carboplatin (CP) as first-line treatment for epithelial ovarian cancer (EOC). Methods: Patients with stage IC to IV EOC, fallopian tube cancer, or primary peritoneal cancer were eligible for enrolment in this open-label, randomized controlled trial at 20 centers in China. Patients were randomly assigned 1:1 to CD group (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) or CP group (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for 3-6 cycles. The primary end point was progression free survival (PFS); secondary end points were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: Between March, 2019 to December, 2021, 395 patients were enrolled, of whom 391 patients were analyzed (195 assigned to CD, 196 to CP). Baseline characteristics were balanced between the two treatment groups. The median follow-up was 21.6 months for the CD group and 22.5 months for the CP group. There was no significant difference in PFS between the two arms (P=0.516); the median PFS was 28.1 months and 30.1 months in the CD and CP arms, respectively. OS data were immature at data cutoff, with a total of 26 deaths in the two treatment groups. In patients with at least one measurable lesion at baseline, ORR was 65.5% in the CD arm and 66.2% in the CP arm (P= 0.941); DCR was 74.1% and 73.8% in the CD and CP arms, respectively (P= 0.971). Among patients who were evaluable by GCIG CA125 criteria, CA125 response was obtained in 86.0% and 88.5% of patients in the CD and CP arms, respectively (P=0.560). More frequent grade 1 to 3 alopecia (32.1% vs 12.3%) and neurotoxicity (20.4% vs 0%) were observed in the CP arm; more hand-foot syndrome (grade 1 to 3, 10.8% vs 2.6%), and oral mucositis (grade 1-3, 12.8% vs 5.1%) in the CD arm. Conclusions: The efficacy of CD regimen is comparable to that of CP, with less alopecia and neurotoxicity. CD may be an alternative first-line treatment for EOC. However, survival data are not yet mature, and longer follow-up is needed. Clinical trial information: NCT03794778 .

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer.

Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC. Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed. Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS. ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Cost-effectiveness analysis of sugemalimab in combination with chemotherapy as first-line treatment in Chinese patients with metastatic NSCLC

IntroductionBecause of its low immunogenicity and associated risk of toxicity, sugemalimab is expected to reshape the first-line treatment landscape for non-small cell lung cancer (NSCLC) in China. However, it remains unclear whether the use of expensive sugemalimab is cost-effective in this population. MethodsA Markov model was constructed based on the GEMSTONE-302 study to assess the efficacy of sugemalimab in combination with chemotherapy for first-line treatment of metastatic NSCLC. Efficacy and safety data were entered, with costs and utility values derived from the literature, and incremental cost-effectiveness ratios (ICERs) were estimated, and univariate sensitivity analyses and probabilistic sensitivity analyses were performed. We also considered cost-effectiveness in two different treatment regimen scenarios after disease progression. ResultsCompared with the placebo plus platinum-based chemotherapy, patients with metastatic NSCLC treated with sugemalimab plus platinum-based chemotherapy saw an increase of 0.56 life-years (LYs) and 0.41 quality-adjusted life-years (QALYs), and patients with squamous NSCLC resulted in an ICER per QALY of $45,280.02. Patients with nonsquamous metastatic NSCLC resulted in an ICER of $45,294.15 per QALY. Univariate sensitivity analysis showed that disease-free survival utility had the greatest impact on the results. Probabilistic sensitivity analysis (PSA) showed that when the willingness-to-pay (WTP) for QALYs was $27,354/QALY, sugemalimab, in combination with platinum-based chemotherapy, was more cost-effective than the placebo. ConclusionFrom a Chinese health care system perspective, first-line treatment of squamous or nonsquamous metastatic NSCLC with sugemalimab plus platinum-based chemotherapy may have cost-effectiveness compared with placebo plus platinum-based chemotherapy at a WTP threshold of $27,354/QALY.

Economic evaluation of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for the treatment of first-line advanced or metastatic squamous NSCLC.

Background and objectiveSintilimab has superior efficacy and safety in patients with advanced or metastatic squamous non-small cell lung cancer (NSCLC), but its cost-effectiveness in China is unclear. This study is to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. pembrolizumab plus chemotherapy for locally advanced or metastatic squamous NSCLC in China.MethodsFrom the perspective of the Chinese health system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime time horizon. The two-stage method was used to estimate the overall survival hazard ratios to avoid the bias by crossover design in ORIENT-12 and KEYNOTE-407 studies. The anchored matching adjusted indirect comparison method (MAIC) was used for indirect comparison based on the individual patient data from ORIENT-12 and the publicly published KEYNOTE-407 study due to the lack of head-to-head clinical trials. Only direct medical costs were included, and utilities were derived from the published literature in the base case analysis. Sensitivity analysis was also performed to verify the robustness of the model results. In addition, the scenario analysis where the utilities were derived from the Quality of Life Questionnaire-Core 30 (QLQ-C30) scale in the ORIENT-12 by mapping to the EuroQol-5-dimension 5-level (EQ-5D-5L) was carried out to explore the uncertainty of the results.ResultsCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy incurred a lower lifetime cost ($12,321 vs. 36,371) and yielded fewer quality-adjusted life-years (QALYs) (0.9902 vs. 1.0085), which resulted in an incremental cost-effectiveness ratio (ICER) of $1,314,208/QALY. A sintilimab strategy is a cost-effectiveness option under the WTP of 1–3 times the GDP per capita in China ($11,250/QALY~$33,749/QALY). The utility value of the post-progression, the unit cost of albumin paclitaxel, and the utility value of the progression-free state were the main drivers in the deterministic sensitivity analysis (DSA). According to the probabilistic sensitivity analysis (PSA), sintilimab + chemotherapy was 100% cost-effective when the WTP was 1–3 times China's per capita GDP. The results of the scenario analysis showed that sintilimab + chemotherapy obtained more QALYs (1.2319 vs. 1.1815) and lower costs ($12,321 vs. 36,371), which implied that sintilimab + chemotherapy may dominate the pembrolizumab + chemotherapy.ConclusionCompared with pembrolizumab + chemotherapy, sintilimab + chemotherapy is more cost-effective for first-line treatment in Chinese patients with locally advanced or metastatic squamous NSCLC.

PB2080: EFFICACY AND SAFETY OF BENDAMUSTINE-BASED REGIMENS AS FIRST-LINE TREATMENT FOR INDOLENT B-CELL NON-HODGKIN LYMPHOMA: A PROSPECTIVE, MULTICENTER, REAL-WORLD STUDY IN CHINA

Background: Indolent non-Hodgkin lymphoma is typically responsive to initial immune-chemotherapy, but it is also prone to persistent recurrence. Bendamustine, an alkylating agent with properties of a purine analog, has been approved for first-line treatment of indolent non-Hodgkin lymphoma in Japan. Although China has approved the second-line treatment of bendamustine for indolent B-cell non-Hodgkin lymphoma in 2019, evidence of bendamustine as first-line treatment for this patient population in China is still scanty currently. Aims: To evaluate the efficacy and safety of bendamustine-based regimens as first-line treatment for Chinese patients with indolent B-cell non-Hodgkin lymphoma in real-world setting. Methods: Treatment-naïve patients with indolent B-cell non-Hodgkin lymphoma were enrolled in this prospective, multicenter, single-arm, real-world study (ChiCTR2000039605). Eligible patients will be given 4-6 cycles (4 weeks/cycle) of bendamustine-based regimens including bendamustine monotherapy (90 mg/m2 on Day 1-2), bendamustine (90 mg/m2 on Day 1-2) plus rituximab (375 mg/m2 on Day 1), bendamustine (70 mg/m2 on Day 1-2) plus rituximab and cytarabine (500 mg/m2 on Day 2-4), or bendamustine (90 mg/m2 on Day 1-2) plus rituximab and bortezomib (1.6 mg/m2 on Day 1, 8 and 15). Tumor response was assessed by independent central review according to Lugano 2014 response criteria. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR) and safety. Results: Between December 2019 and February 2022, 29 patients were enrolled in this study. The median age of the 29 patients was 63.0 years (range, 35.0-83.0 years). Majority of patients were female (17/29, 58.6%), had stage II-IV disease (23/29, 79.3%), had an International Prognostic Index (IPI) score of 0-2 (20/29, 69.0%), and had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 (21/29, 72.4%). Sixteen patients (55.2%) completed 6 cycles of treatment, and 22 patients (75.9%) completed 4-6 cycles of treatment. Of the 29 patients, 19 (65.5%) achieved a complete response, 5 (17.2%) achieved a partial response, 1 (3.5%) had a stable disease, and 4 unknown (13.8%). The ORR and DCR were 82.8% (95% CI, 64.2-94.2%) and 86.2% (95% CI, 68.3-96.1%), respectively. Hematological and non-hematological adverse events were reported in 75.9% and 17.2% of patients, respectively. Summary/Conclusion: Bendamustine-based regimens as first-line treatment were effective and well-tolerated in patients with indolent B-cell non-Hodgkin lymphoma, suggesting that this first-line regimen might offer a potential therapeutic option for this patient population in China.

Cost-Effectiveness of Bevacizumab Biosimilar LY01008 Combined With Chemotherapy as First-Line Treatment for Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small Cell Lung Cancer.

Objective: To investigate whether LY01008, a locally developed bevacizumab biosimilar agent, is appropriate for widespread use among Chinese advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC) patients, our current study was designed to evaluate the cost-effectiveness of first-line LY01008 combined with platinum-doublet chemotherapy versus chemotherapy alone from the perspective of the Chinese healthcare system. Material and Methods: This economic evaluation designed a Markov model to compare the healthcare cost and quality-adjusted life-year (QALY) of first-line LY01008 combined with chemotherapy versus first-line chemotherapy. Transition probabilities, including disease progression, survival, and adverse event (AE)-related discontinuation of first-line treatment, were estimated using data from the clinical trials. Costs and health utilities were derived from local databases, hospitals, and published literature. Our base case analysis and scenario analysis focused on the cost-effectiveness of chemotherapy combined with a clinical trial dosage (15 mg/kg every 3-week cycle) and a real-world dosage (7.5 mg/kg every 3-week cycle) of LY01008, respectively. Results: In the base case analysis, first-line LY01008 combined with chemotherapy was associated with an increase of 0.48 QALYs in effectiveness and an increase of CNY 189,988 (US$ 26,240) in healthcare costs compared with first-line chemotherapy, resulting an incremental cost-effectiveness ratio (ICER) of CNY 375,425 (US$ 54,430)/QALY. In the scenario analysis, first-line LY01008 combined with chemotherapy was associated with a mean healthcare cost of CNY 265,060 (US$ 38,429), resulting an ICER of CNY 221,579 (US$ 32,125/QALY) between first-line LY01008 combined with chemotherapy versus first-line chemotherapy. The parameters that determine the cost of LY01008 have the greatest impact on the cost-effectiveness results. Conclusion: From the perspective of the Chinese healthcare system, first-line LY01008 at a real-world dosage combined with chemotherapy is likely to represent a cost-effective strategy compared with first-line chemotherapy alone for Chinese advanced or recurrent nonsquamous NSCLC patients.

Rituximab-Based Regimen As First-Line Treatment in Chinese Patients with Follicular Lymphoma: Three-Year Safety Data from a Prospective, Observational Study

Background:A number of international randomized clinical trials have demonstrated the efficacy of rituximab when added to existing chemotherapy regimens such as CHOP for the first line treatment of follicular lymphoma (FL) without inducing significant toxicity. Base on the published clinical evidences, rituximab-based regimen (R-chemo) was recommended for treating FL patients in China. Due to the low incidence of FL in China, the knowledge on safety and effectiveness of R-chemo in Chinese patients is scarce.Methods:This open-label, single-arm, multicenter, non-interventional study (NCT01340443) was designed to assess the safety and effectiveness of R-chemo in Chinese patients with FL. FL patients who were eligible to receive R-chemo (CHOP or non-CHOP) as first-line treatment were enrolled with no specific exclusion criteria. Individual dose and duration of treatment was determined at the investigator's discretion, local labeling information and standard clinical practice. Patients went through safety and efficacy assessment after the last rituximab dose was administered, and then followed-up for 3 years. The primary endpoints included adverse events (AEs), severe adverse events (SAEs), adverse drug reactions (ADRs), and adverse events of special interest (AESIs). Data for analyses were collected from medical records. This study was registered in clincialtrials.gov (NCT01340443).Results:A total number of 31 patients were enrolled by 12 sites. Twenty-three patients completed the study procedures. Twenty-nine patients received at least one cycle of rituximab and completed at least one tumor assessment after baseline, and they were included in the effectiveness analysis. The average age of these FL patients was 53.3 (12.25) years old. 72.4% of them were below 60 years old.Safety analysis was performed in 31enrolled patients as they received at least one dose of rituximab. Twenty-eight (90.3%) FL patients reported 202 AEs (table 1). The shortest median duration was 1 day, reported from infusion related reaction. Sinus bradycardia associated with the longest median duration, which was 1446.0 days. Forty-one AEs in 18 (58.1%) FL patients were reported as drug (rituximab) related AEs. The most common drug-related AEs which had CTC ≥ 3 were bone marrow failure (6.5%), agranulocytosis (3.2%), lung infection (3.2%), upper respiratory tract infection (3.2%), white blood cell count decreased (3.2%), neutrophil count decreased (3.2%), and enteritis (3.2%). Drug-related AEs of special interest were infusion related reactions (6.5%) and other opportunistic infections (6.5%). Four (12.9%) FL patients reported 5 SAEs, while 4 cases were drug-related SAEs. The AE which led to death in FL patient was intestinal perforation (1 case) and was not related to observational drug. In term of effectiveness, final analysis showed that 2-year progression-free survival rate was 61% and the 2-year overall survival rate was 97%.Summary:This study further validated the safety and effectiveness of R-chemo in Chinese FL patients in real-life clinical practice. Safety profile of R-chemo was acceptable when it was used as first-line treatment. Good effectiveness was also achieved, although the patient number was limited. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and acquired resistance of EGFR-TKI combined with chemotherapy as first-line treatment for Chinese patients with advanced non-small cell lung cancer in a real-world setting

BackgroundTo compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.MethodsThis retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.ResultsThe median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.67–23.33] vs. 11.70 months [95% CI, 10.81–12.59], p < 0.001). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.30–41.70) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898).ConclusionsCompared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

Oral vinorelbine versus intravenous vinorelbine, in combination with epirubicin as first-line chemotherapy in Chinese patients with metastatic breast cancer

Oral VRL offers easier administration, better quality of life, and cost saving. This study aimed to evaluate the treatment efficacy in terms of tumor response of the two formulations of vinorelbine (VRL, oral and IV) in combination with epirubicin (EPI); and the effect of EPI co-administration on VRL pharmacokinetics (PK) in Chinese patients with metastatic breast cancer (MBC) using a phase 2, open label, randomized trial. Patients were aged 18–70 years, had histologically confirmed MBC, Karnofsky Performance Status ≥ 70%, and life expectancy ≥ 12 weeks. The treatment consisted of 6 cycles of 3 weeks each. VRL dose was: (Oral-VRL) 60 mg/m2 for cycle 1, 80 mg/m2 for cycles 2–6, and (IV-VRL) 25 mg/m2 for cycle 1 and 30 mg/m2 for cycles 2–6. EPI dose of 75 mg/m2 was given on day 1 in both arms for all cycles. 133 patients were enrolled: 66 in Oral-VRL and 67 in IV-VRL arms. The median age for Oral-VRL and IV-VRL arms was 48.4 and 50.0 years, respectively. Objective response rates were 50.0% (95% CI 37.4–62.6%) for Oral-VRL and 53.7% (95% CI 41.1–66.0%) for IV-VRL. Both treatment arms met the efficacy objective target of at least 31 responses, demonstrating efficacy as first-line treatment for MBC. Similar blood PK profiles, exposures, and VRL clearance were observed between VRL + EPI vs VRL-only modalities for both arms. Oral VRL is comparable to IV VRL and an effective first-line treatment for Chinese patients with MBC. The activity of VRL + EPI combination is unaltered when VRL is given orally at recommended doses.

Dose-finding study of modified FLOT (mFLOT) regimen as first-line treatment in Chinese patients with metastatic adenocarcinoma of stomach.

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of modified FLOT regimen (fluorouracil plus leucovorin, oxaliplatin and docetaxel) for treating Chinese patients with metastatic adenocarcinoma of stomach. Chinese patients with untreated advanced or metastatic stomach adenocarcinoma were enrolled. Docetaxel (D), oxaliplatin (O) and leucovorin were administrated intravenously on day 1. Fluorouracil (F) was administrated continuous intravenously on day 1 for 48h. The treatment was repeated every 2weeks. The start doses of docetaxel and oxaliplatin were 40mg/m2 and 65mg/m2, respectively. Dose escalation followed a 3 + 3 design. Total 6 dose levels were set to determine the MTD and RD. Fluorouracil and leucovorin were given as fix doses at 2200mg/m2 and 200mg/m2, respectively. Adverse events that occurred in the first 2 cycles were recorded to determine dose-limiting toxicity (DLT). The primary endpoints were MTD and RD determination. A total of 18 patients were treated in 5 dose levels. DTL occurred in one patient of level 4 (grade 3 hypophosphatemia). Other 3 patients were enrolled in level 4 and no DLTs were observed. In level 5, 2 patients suffered grade 4 neutropenia after first cycle of treatment and were defined as DLTs. Therefore, level 5 (D/O/F: 50/75/2200mg/m2) was defined as MTD and level 4 (D/O/F: 45/75/2200mg/m2) was defined as RD. Common adverse events in first two cycles were nausea, anorexia, leukopenia, neutropenia and anemia. For 16 patients assessable for tumor response, 7 patients had partial response (43.7%) and 5 experienced stable disease. Disease control rate were 75% (12/16). Two patients underwent conversion operation after 6 cycles of treatment. One pathological complete response (case in level 3) and one pathological partial response (case in level 2) were observed. Median progression-free survival was 4.4months (95% CI 2.9-5.9months) in 14 patients. The RD of modified FLOT regimen in Chinese patients with advanced gastric cancer was docetaxel 45mg/m2, oxaliplatin 75mg/m2, leucovorin 200mg/m2 and fluorouracil 2200mg/m2 on day 1 of every 14-day cycle. Its efficacy will be assessed by further phase II study.

Efficacy of platinum-based regimens as the first-line therapy in Chinese patients with advanced TNBC and deleterious BRCA1/2 mutations.

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.

P1.01-112 Osimertinib vs Standard of Care (SoC) EGFR-TKI as First-Line Treatment in Chinese Patients With EGFRm Advanced NSCLC

P1.01-112 Osimertinib vs Standard of Care (SoC) EGFR-TKI as First-Line Treatment in Chinese Patients With EGFRm Advanced NSCLC

P1.04-36 Tislelizumab Combined With Chemotherapy as First-Line Treatment in Chinese Patients With Advanced Lung Cancer

P1.04-36 Tislelizumab Combined With Chemotherapy as First-Line Treatment in Chinese Patients With Advanced Lung Cancer

Cost Effectiveness of Imatinib, Dasatinib, and Nilotinib as First-Line Treatment for Chronic-Phase Chronic Myeloid Leukemia in China.

Tyrosine kinase inhibitors (TKIs) have obvious effects on chronic myeloid leukemia (CML), but they are expensive in China. Moreover, the overall cost of treatment of CML is high and the medical economic burden of patients with CML on the government is heavy. This study tested the cost effectiveness of imatinib, nilotinib, and dasatinib as first-line treatment in Chinese patients who were first diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). A state-transition Markov model combining clinical effectiveness, utility, and cost data was used. Sensitivity analyses were conducted to determine the robustness of the model outcomes. The imatinib-first, dasatinib-first, and nilotinib-first strategy offered patients 9.76, 9.87, and 9.72 quality-adjusted life years (QALYs) at a cost of US$303,502.42, US$381,681.03, and US$305,509.92 over 20years, respectively. The nilotinib-first strategy exhibited the lowest utility and highest price and was thus eliminated. An incremental cost-effectiveness analysis of the imatinib-first strategy and the dasatinib-first strategy showed that the dasatinib-first strategy yielded an incremental cost-utility ratio (ICER) of 710,714.64 $/QALY compared with the imatinib-first strategy, which exceeded the threshold; hence, the dasatinib-first strategy was not cost effective and was eliminated. The results were robust for multiple sensitivity analyses. From the perspective of the Chinese medical system, imatinib is likely to be more cost effective than dasatinib and nilotinib for patients who were first diagnosed with CML-CP.

Clinical effect of pemetrexed as the first-line treatment in Chinese patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

BackgroundThe efficacy of pemetrexed‐based first‐line chemotherapy in anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC) has been demonstrated in several studies; however, there is a lack of data from Chinese populations.MethodsThe clinicopathological characteristics and treatment outcomes of 52 patients with ALK‐positive advanced NSCLC who received pemetrexed as first‐line chemotherapy at the Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively reviewed. The primary end points were response rate and progression‐free survival (PFS).ResultsThe gender proportion was balanced and the median age was 51 years (range 26–76). Of the 52 patients, 46 (88.5%) had stage IV disease, predominantly adenocarcinoma (98.1%). Sixteen patients were current/former smokers and 36 were never/light smokers. The most common sites of metastasis were the pleura (36.5%), bone (30.8%), lung (26.9%), and brain (17.3%). The median PFS was 9.5 months (95% confidence interval 7.454–11.536). At the time of analysis, partial remission was achieved in 18 (34.6%) patients, stable disease in 26 (50.0%), and progressive disease in eight (15.4%); none of the patients achieved complete remission. The objective response rate was 34.6% and the disease control rate was 84.6%. Common adverse events with pemetrexed were neutropenia (53.8%), nausea and vomiting (51.9%), leukopenia (32.7%), and fatigue (25.0%), mainly at grades 1 or 2.ConclusionsPemetrexed is efficient and tolerated as first‐line treatment for ALK‐positive NSCLC in a cohort of Chinese patients and may prove to be an alternative option for the treatment of ALK‐positive NSCLC.

Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer

ObjectivesRetrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB. Materials and methodsChinese patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned (1:1) to 6 cycles maximum (21 days/cycle) of pemetrexed 500mg/m2+cisplatin 75mg/m2 (day 1), or gemcitabine 1250mg/m2 (days 1 and 8)+cisplatin 75mg/m2 (day 1). ResultsIn JMIL, 256 Chinese patients were randomized (PC, n=126; GC, n=130). Patient baseline characteristics were balanced between treatment arms. In the combined dataset, PC was superior to GC in prolonging OS, with adjusted hazard ratio (HR) of 0.87 (95% CI: 0.77–0.98, p=0.023) and median OS of 11.76 versus 10.94 months. In the JMIL-only population, no significant OS difference observed between treatment arms (adjusted HR=1.03 [95% CI: 0.77–1.39, p=0.822]; unadjusted HR=0.996 [95% CI: 0.74–1.33, p=0.980]), nor for other secondary efficacy endpoints. Significantly fewer patients in the PC arm experienced drug-related grade 3/4 toxicities, 54 (43.2%) versus 71 (55.9%) for GC (p=0.045), with significantly lower rates of leukocytopenia, thrombocytopenia, and fatigue. ConclusionThis study showed that in the combined population, OS of PC was superior to GC, while in the Chinese-only population, no significant difference was observed; a better safety and risk/benefit profile was found in the PC arm. A PC regimen should be considered as a standard of care in Chinese nonsquamous NSCLC patients in a first-line setting.