Previous Chemotherapy Regimens Research Articles

Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients (pts) with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial.

1101 Background: SG is a Trop-2 directed antibody-drug conjugate approved for pts with advanced, pretreated, triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer. The most common SG-related adverse events (AEs) are neutropenia and diarrhea which can lead to treatment modifications. Granulocyte colony-stimulating factor (G-CSF) and loperamide (L) are frequently used for managing these AEs. PRIMED is assessing if primary prophylaxis with G-CSF and L can improve the tolerability of SG. Methods: PRIMED (NCT05520723) is an open-label, single-arm, phase II trial. Pts had received between 1-2 previous chemotherapy regimens for ABC, including a taxane in any setting, unless contraindicated. HR+/HER2- pts had to be endocrine-resistant. Pts received SG (10 mg/kg IV, d 1 and 8, every 21 d) until disease progression (PD) or unacceptable toxicity. G-CSF (0.5 MU/kg/day SC, d 3, 4, 10, and 11) and L (2 mg orally, twice a day or 4 mg QD, d 2, 3, 4, 9, 10, and 11) were given during the first two cycles. The primary endpoints were incidence of ≥ grade (G) 3 neutropenia (H0: ≥40%; H1: ≤22%) or ≥ G 2 diarrhea (H0: ≥25%; H1: ≤10%) after two cycles. Results: A total of 50 pts were enrolled between February 2023 and September 2023 (TNBC, n = 32 [64%]). At data cut-off on October 18, 2023 (median follow-up, 4.3 months), 31 pts remained on treatment. The main reason for treatment discontinuation was PD, which was reported for 16 pts. After the first two cycles, incidence of any G neutropenia and diarrhea were 28% and 34%, respectively. Eight pts (16%) had ≥ G 3 neutropenia, meeting this primary endpoint (p=0.0002). Eight pts (16%) had ≥ G 2 diarrhea (4% G 3), showing numerical benefit of prophylactic L (p=0.084). No pts developed febrile neutropenia. The overall rate of AEs associated with dose reductions and treatment interruptions was 18% and 44%, respectively. No treatment discontinuations due to AEs were reported. Conclusions: Prophylactic administration of G-CSF and L resulted in a clinically relevant reduction of the incidence and severity of SG-related neutropenia and diarrhea and limited AE related dose reductions/interruptions and treatment discontinuations. Clinical trial information: NCT05520723 .

Number of lines of previous chemotherapy regimen might affect the oucome of sacituzumab govitecan in metastatic triple-negative breast cancer patients.

Number of lines of previous chemotherapy regimen might affect the oucome of sacituzumab govitecan in metastatic triple-negative breast cancer patients.

Clinical characteristics and risk factors for oxaliplatin hypersensitivity reactions in patients with colorectal cancer

Introduction Oxaliplatin is an anticancer drug used primarily for cancers of the gastrointestinal tract, and oxaliplatin hypersensitivity reaction is a rare but serious side effect. This study aimed to identify the clinical characteristics and risk factors for oxaliplatin hypersensitivity reactions in patients with colorectal cancer. Methods This retrospective study included 280 patients who developed oxaliplatin hypersensitivity reactions and 476 patients who did not. Results Logistic regression analysis indicated that a history of allergy (odds ratio (OR) = 2.232, 95% confidence interval (CI) (1.209, 4.119), P = .010), previous oxaliplatin exposure (OR = 8.081, 95% CI (3.024, 21.593), P < .001), and chemotherapy regimen (OR = 2.148, 95% CI (1.411, 3.271), P < .001) were risk factors for oxaliplatin hypersensitivity reactions. These reactions averaged 7.29 ± 2.78 (median 7, 1–16) cycles, with a mean cumulative dose of 589.53 ± 274.43 mg. Grade 2 oxaliplatin hypersensitivity reactions were the most common, occurring in 197 patients (70.4%), followed by grade 3 reactions in 68 patients (24.3%), and grade 4 reactions in 9 patients (3.2%). The most common symptom of oxaliplatin hypersensitivity reactions was itching (211 patients, 75.4%), followed by facial flushing (133 patients, 47.5%), and chest discomfort (77 patients, 27.5%). Conclusions We identified a history of allergy to previous oxaliplatin exposure and chemotherapy regimens as risk factors for oxaliplatin hypersensitivity reactions. Healthcare providers should be aware of the risk factors for oxaliplatin hypersensitivity reactions and carefully monitor patients receiving oxaliplatin.

Real Event Analysis of the Efficacy and Safety of Polatuzumab Vedotin Combination Regimen in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Abstract： Objective Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodges lymphoma (NHL) subtype, although R⁃CHOP treatment cured about 60% of patients. However, 40%-45% of patients do not respond to first-line therapy or relapse after an initial response, and this segment of patients has a poor prognosis. Therefore, the use of targeted drugs and the exploration of drug combination schemes are particularly important, among them, anti-CD79B antibody-drug conjugate (ADC) polatuzumab vedotin (Pola) combined with Bendamustine-Rituximab (BR) and Pola combined with R-CHOP are promising therapeutic options. To analyze the efficacy and safety of Pola combined with BR and Pola combined with R-CHOP in the treatment of relapsed/refractory DLBCL (R/R DLBCL). Methods The single-arm, Phase II clinical study commenced at our center in May 2023. Eligible patients were R/R DLBCL patients with Ann Arbor stages 3-4, ages 36 to 88 years, who had received at least one previous standard chemotherapy regimen. The clinical data of 17 patients enrolled in our center from May 2023 to August 2023 were retrospectively analyzed, including 10 males and 7 females. The median age was 69 (ranged 36-88) years. 12 patients were treated with Pola-BR and 5 with Pola-R-CHOP, the clinical characteristics, medication regimen, efficacy and occurrence of adverse reactions were analyzed. To explore the causes of adverse reactions between the Polar-BR group and the Polar-R-CHOP group. Results Data as of August 1, 2023, in the efficacy evaluation of 17 patients, the overall response rate (OR) was 71% (12/17) and the complete response (CR) rate was 53% (9/17). Progressive free survival (PFS), median follow-up of 45 days, with 3 cases (12%) experiencing disease progression. Compared with the Pola-BR group, the Pola-RCHOP group had a lower incidence of adverse reactions. The main adverse event was a pulmonary infection, of which 33% (4/12) were in the Polar-BR group and 25% (1/5) were in the Polar-R-CHOP group, and no severe pneumonia occurred in either group. Conclusion Compared with the traditional R-CHOP regimen, Polar+BR/RCHOP has better therapeutic effect and a better application prospects for R/R DLBCL patients.

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial

Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables. In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2- locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with ClinicalTrials.gov, NCT03901339. At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4-18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0-15·7] vs 11·2 months [10·1-12·7]; hazard ratio [HR] 0·79, 95% CI 0·65-0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03-2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months vs 3·0 months; HR 0·75 [0·61-0·92]; p=0·0059) and fatigue (median 2·2 months vs 1·4 months; HR 0·73 [0·60-0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2- metastatic breast cancer. Gilead Sciences.

Pertuzumab retreatment in patients with HER2-positive locally advanced/metastatic breast cancer: Overall survival results of a phase III randomized trial (JBCRG-M05: PRECIOUS).

1015 Background: We previously reported that pertuzumab (P) retreatment in combination with trastuzumab (T) + chemotherapy based on physician’s choice (C) (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with T + C (TC) in patients with HER2-positive locally advanced/metastatic breast cancer (LA/MBC) previously treated with P-containing regimens in the phase III PRECIOUS study. Here we report updated OS at the median follow-up of 27.4 mo. Methods: Patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC were randomly assigned 1:1 to two groups, PTC group and TC group, stratified by estrogen receptor (ER) status, previous treatment duration of P, number of previous chemotherapy regimens, and presence or absence of visceral metastasis. The primary endpoint was investigator-assessed PFS. The key secondary endpoints included OS, independent reviewer assessed PFS and safety. Superiority of PTC to TC will be tested using a log-rank test and a one-sided P-value of less than 0.05 will be considered an indicator of superiority. The distribution of OS will be estimated using the Kaplan-Meier method. In addition, the hazard ratio and one-sided 95% CI of the therapeutic effect between the groups will be calculated using the Cox proportional hazard model. Results: Of the 219pts enrolled, 217 (108 PTC, 109 TC) were included in the intent-to-treat analysis. At the data cutoff (Dec 31, 2021), OS and PFS events were 138 (63.6%) and 190 (87.6%), respectively. Updated median OS was significantly longer in the PTC group (median OS 36.2 vs. 26.5 mo.; HR = 0.73 [one side 95%CI upper limit, 0.97]; log-rank test p = 0.0323). In a prespecified subgroup analysis for OS including ER, visceral metastases, number of previous chemotherapy regimen was broadly constant without disease-free interval. Updated median investigator-assessed PFS (5.5 vs. 4.2 mo.; HR = 0.81 [one side 95%CI upper limit, 1.03]; stratified log-rank test p = 0.019) were also significantly better in the PTC group. Median PFS by independent review did not show the difference between two groups (4.4 vs. 4.4 mo.; HR = 1.03 [one side 95%CI upper limit, 1.36]; log-rank test p = 0.561). The serious adverse event rate did not differ between the groups (19.0% vs. 23.1%). There were no new safety signals in the two groups. Conclusions: Retreatment of P in combination with TC demonstrated significantly improved OS compared to TC. HER2 dual blockade with PT can contribute to improve survival in patients previously treated with P-containing regimens as 1st/2nd-line treatment for LA/MBC. Clinical trial information: NCT02514681 .

Activity of TNT: a phase 2 study using talimogene laherparepvec, nivolumab and trabectedin for previously treated patients with advanced sarcomas (NCT# 03886311).

Intratumoral injection of talimogene laherparepvec evokes a cytotoxic immune response. Therefore, the combination of talimogene laherparepvec with trabectedin and nivolumab may have synergistic effects in advanced sarcomas. This phase 2 trial was conducted from May 30, 2019 to January 31, 2022. Endpoints: Primary: Progression free survival rate at month 12. Secondary: Best overall response, progression free survival rate at 6 and 9 months, overall survival rate at 6, 9, and 12 months, incidence of conversion of an unresectable tumor to a resectable tumor, and incidence of adverse events. Eligible patients had to be ≥ 18 years of age, have advanced histologically proven sarcoma, at least 1 previous chemotherapy regimen, and at least one accessible tumor for intratumoral injection. Treatment: Trabectedin intravenously (1.2 mg/m2 q3 weeks), nivolumab intravenously (3 mg/kg q2 weeks), and intratumoral talimogene laherparepvec (1x108 plaque forming units/ml q2 weeks). Median time of follow-up: 15.2 months. Efficacy analysis: Thirty-nine patients who had completed at least one treatment cycle and had a follow-up computerized tomography were evaluable for efficacy analysis. Median number of prior therapies: 4 (range 1-11). Progression free survival rate at month 12, 36.7%. Confirmed Best Overall Response by Response Evaluation Criteria in Solid Tumors v1.1 = 3 partial responses, 30 stable disease, 6 progressive disease. Best Overall Response Rate, 7.7%, Disease Control Rate, 84.6%; median progression free survival, 7.8 (95% Confidence Intervals: 4.1-13.1) months; 6-, 9-, 12-month progression free survival rates, 54.5%/45.9%/36.7%; median overall survival 19.3 (95% Confidence Intervals: 12.8 -.) months; 6-, 9- and 12-month overall survival rate, 86.9%/73.3%/73.3%. One patient had a complete surgical resection. Fifty percent of patients had a ≥ grade 3 treatment related adverse events which included anemia (6%), thrombocytopenia (6%), neutropenia (4%), increased alanine transaminase (4%), decreased left ventricular ejection fraction (4%), dehydration (4%), hyponatremia (4%). Taken together these data suggest that the TNT regimen is effective and safe for advanced previously treated sarcomas, and is worth being further studied in a randomized phase 3 trial as first- or second- line treatment for patients with advanced sarcomas.

Trifluridine–Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer

BackgroundIn a previous phase 3 trial, treatment with trifluridine–tipiracil (FTD–TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD–TPI in addition to bevacizumab has the potential to extend survival.MethodsWe randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD–TPI plus bevacizumab (combination group) or FTD–TPI alone (FTD–TPI group). The primary end point was overall survival. Secondary end points were progression-free survival and safety, including the time to worsening of the Eastern Cooperative Oncology Group (ECOG) performance-status score from 0 or 1 to 2 or more (on a scale from 0 to 5, with higher scores indicating greater disability).ResultsA total of 246 patients were assigned to each group. The median overall survival was 10.8 months in the combination group and 7.5 months in the FTD–TPI group (hazard ratio for death, 0.61; 95% confidence interval [CI], 0.49 to 0.77; P<0.001). The median progression-free survival was 5.6 months in the combination group and 2.4 months in the FTD–TPI group (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.54; P<0.001). The most common adverse events in both groups were neutropenia, nausea, and anemia. No treatment-related deaths were reported. The median time to worsening of the ECOG performance-status score from 0 or 1 to 2 or more was 9.3 months in the combination group and 6.3 months in the FTD–TPI group (hazard ratio, 0.54; 95% CI, 0.43 to 0.67).ConclusionsAmong patients with refractory metastatic colorectal cancer, treatment with FTD–TPI plus bevacizumab resulted in longer overall survival than FTD–TPI alone. (Funded by Servier and Taiho Oncology; SUNLIGHT ClinicalTrials.gov number, NCT04737187; EudraCT number, 2020-001976-14.)

A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients.

Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.

Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention.

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

Combination therapy of oral cyclophosphamide and bevacizumab for patients with recurrent ovarian and peritoneal cancer

Chemotherapy for patients with recurrent cancer aims to obtain survival benefits, relieve symptoms, and improve quality of life. We used oral cyclophosphamide and bevacizumab (BEV) combination therapy in recurrent ovarian and peritoneal cancer cases, where standard chemotherapy was infeasible. Subsequently, we evaluated the safety and efficacy of this treatment. Between August 2014 and June 2020, patients received the following regimen: oral cyclophosphamide 50 mg daily and intravenous cyclic BEV 15 mg/kg every 3 weeks. Data from 2 facilities were retrospectively analyzed. Twenty-two patients were enrolled (20 with ovarian cancer and two with peritoneal cancer). The median follow-up period and age were 18.9 months (range, 5.0-51.5) and 60 years (range 37-81), respectively. Sixteen patients had platinum resistance. The median number of previous chemotherapy regimens was 2.5 (range 0-5). The median implementation cycle was five (range 2-14). Eighteen patients discontinued treatment due to side effects (3 patient) and disease progression (15 patient). Grade 2 toxicities included neutropenia (1 patient), proteinuria (1 patient), hypertension (2 patient), and esophagitis (1 patient). Two patients had complete response and one had a partial response. Five patients had stable disease. The response rate in platinum-sensitive recurrence was 33.3%, and 7.1% in platinum-resistant recurrence, and a clinical benefit was found in 8 (36.3%) patients. The median PFS and overall survival from cyclophosphamide and BEV initiation was 5.3 months (range, 0.8-23.5) and 9.2 months (range, 4.8-51.5), respectively. The combination of oral cyclophosphamide and BEV does not have a high response rate, but is well-tolerated and can be used safely in patients who are difficult to treat after second-line chemotherapy. Data from 2 facilities were retrospectively analyzed.

Second-line bevacizumab plus FOLFOX in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-based chemotherapy.

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]

A multi-center effectiveness comparison study of fruquintinib with constructed external control cohort of other targeted kinase inhibitors using real-world data in third-line treatment of metastatic colorectal cancer.

The objective of this study was to assess the comparative efficacy in third-line setting for metastatic CRC (mCRC) patients using matched population of FRESCO trial with fruquintinib and real-world data with other TKIs. The arm of fruquintinib from the FRESCO phase III trial (NCT02314819) included the data of patients with metastatic CRC that progressed after at least two lines of chemotherapy and received fruquintinib treatment. An external control arm was constructed using real-world data (RWD) of patients who received other TKIs based on key eligibility criteria of FRESCO. The baseline characteristics of two arms was balanced by propensity score matching (PSM). The Kaplan-Meier method and Cox proportional hazard model was used to evaluate progression free survival (PFS) and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), respectively. Overall, 128 patients were successfully matched by PSM in each, fruquintinib and other TKIs group. The patients in fruquintinib group showed significant increase in median PFS than other TKIs (3.71 vs. 2.49 months, HR = 0.67, 95%CI, 0.48-0.94, p = 0.019). In the subgroup analysis, fruquintinib showed a significant benefit in PFS compared with other TKIs among patients undergoing two or three previous chemotherapy regimens (HR 0.58, 95%CI 0.40-0.84; p=0.004), with rectum as primary disease site (HR 0.52, 95%CI 0.31-0.87; p=0.013), with left sided primary tumor location (HR 0.62, 95%CI 0.42-0.90; p=0.011), with multiple metastasis sites (HR 0.68, 95%CI 0.48-0.97; p=0.034) and with lung metastasis (HR 0.65, 95%CI 0.43-0.98; p=0.042). With the approach of establishing the external control arm from RWD, this study has demonstrated that treatment with fruquintinib significantly prolonged PFS as compared to other TKIs in patients as third-line mCRC treatment.

Efficacy and safety of anamorelin in patients with cancer cachexia: Post-hoc subgroup analyses of a placebo-controlled study.

Cachexia, a disorder associated with anorexia, inflammation, and muscle wasting, is frequent in cancer patients. We performed post-hoc analyses of the ONO-7643-04 study to investigate the efficacy and safety of anamorelin in subgroups of Japanese patients with non-small cell lung cancer (NSCLC). The patients were divided into subgroups by baseline characteristics, including sex, age, body mass index, prior weight loss, performance status (PS), concomitant anticancer therapy, and number of previous chemotherapy regimens. The changes from baseline through to 12 weeks for lean body mass (LBM), body weight, and appetite were calculated. Appetite was evaluated using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) item 8 score. Responder rates were defined as the maintenance/improvement of LBM (≥0kg), body weight (≥0kg), or QOL-ACD item 8 score (≥0) from baseline to all evaluation time points. Safety was evaluated in patients subgrouped by age and PS. Anamorelin resulted in greater improvements versus placebo in LBM, body weight, and appetite in most subgroups. Anamorelin was also associated with greater LBM, body weight, and appetite responder rates than placebo in nearly all subgroups. Among anamorelin-treated patients, adverse drug reactions (ADRs) tended to be more frequent with increasing age (<65 years, 19.2%; ≥65 to <75 years, 45.9%; ≥75 years, 60.0%) and PS score (PS 0-1, 38.4%; PS 2, 60.0%). The frequency of serious ADRs was 2.7% and 0% in the PS 0-1 and PS 2 subgroups, respectively. This study of NSCLC patients with cancer cachexia revealed consistent improvements in LBM, body weight, and appetite across most subgroups of anamorelin-treated patients. This study also demonstrated the tolerability of anamorelin regardless of age and PS, with a low incidence of serious ADRs in each subgroup.

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy.

Nivolumab improves overall survival (OS) in patients with advanced gastric cancer (AGC) refractory to at least two previous chemotherapy regimens. We investigated whether changes in body weight and nutrition from first-line chemotherapy to nivolumab affected its efficacy. The correlation between weight change and nutritional status up to the start of nivolumab treatment and OS and progression-free survival (PFS) after starting nivolumab treatment was determined. Nutritional status was examined using the C-reactive protein/albumin ratio (CAR). A loss in body weight (LBW) from the onset of the first treatment of <4.5% led to OS prolongation and improved PFS outcomes. The median OS values in the LBW < 4.5% and ≥4.5% groups were 11.4 and 3.6 months, respectively. Similarly, changes in CAR from first-line chemotherapy (ΔCAR) affected OS; the ΔCAR < 0.01 group had a better prognosis than the ΔCAR ≥ 0.01 group. The median OS values in the ΔCAR < 0.01 and ≥0.01 groups were 9.4 and 4.5 months, respectively. The median OS in the group with LBW < 4.5% and ΔCAR < 0.01 was 12.9 months. LBW and deterioration of nutritional status following first-line chemotherapy are poor prognostic factors in AGC patients who received nivolumab as third- or later-line therapy. Early intervention to maintain body weight and nutritional status may improve the efficacy of immune checkpoint inhibitors.

EVALUATION OF BLOOD CELL COUNT USING THE SYSMEX XN-1000 AUTOMATIC HEMATOLOGY ANALYZER TO OPTIMIZE COLLECTION OF PERIPHERAL BLOOD PROGENITOR CELLS BY LEUKAPHERESIS

Autologous stem cell transplantation (ASCT) is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell (HSC) collection. The objective was to identify characteristics that can influence the effectiveness of mobilization and create a model to predict the success of mobilization in candidates for ASCT. This was a retrospective study, and data from patient candidates for ASCT between 09/2015 and 12/2021 were analyzed. Participants were assisted in five hospitals and laboratory procedures were performed at the Cell Processing Center (CPC) of Cetebio/Fundação Hemominas, Brazil. The medical records of the participants were reviewed to obtain the following information: gender, age, weight, diagnosis, mobilization, mobilization cycle, number of previous chemotherapy regimens and previous radiotherapy. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood (PB) blood count. Enumeration of CD34+ cell was performed using the ISHAGE protocol. The blood count was performed using an automated counter (SYSMEX XN-1000 AS-01). The studied outcome, good mobilization, was defined as a viable CD34+ cell count ≥ 20/uL in the PB. Model derivation was performed using logistic regression. The level of classification accuracy of model was tested in a subset of participants. The study population included 807 patients, 413 (51%) of whom were male. The median age was 54 (1-74) years. Multiple myeloma was the most common diagnosis (58,2%), followed by lymphoma. Of the 807 participants, 74 failed in previous mobilization attempts, totaling 881 cycles of mobilizations and collection attempts. Of the 623 participants, 353 were good mobilizers. Increasing patient weight, lower mean corpuscular volume (MCV), higher nucleated red blood cells (nRBC), peripheral blood mononuclear cells (PBMC), and immature granulocyte count were significantly associated with good mobilization. In addition, participants diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma (OR=1.92; 95%CI: 1.21 – 3.05; P=0.006). The model was applied to the validation set to identify patients who underwent apheresis (CD34+ cells count ≥ 10 μL), resulting in a sensibility of 69%, a specificity of 95%, positive predictive value of 98%, a negative predictive value of 50%. The results of our study are extremely relevant to institutions that do not have a flow cytometer and rely on other institutions to define HSC collection by apheresis. Cetebio serves nine transplant centers. The centers that perform the collection of HSC are located between 40 to 568 km away from Cetebio (place of quantification of CD34+ cells). Predicting the outcome of mobilization may allow the adoption of complementary measures, such as the use of plerixafor. Furthermore, it would better optimize the collection of CPH by apheresis. Thus, it would be possible to avoid additional collection days, reducing costs and risks related to administration of additional doses of G-CSF, catheter maintenance and prolonged hospital stay. Success in mobilization was greater in participants who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher weight and levels of nRBC, immature granulocytes, and PBMC, as well as lower levels of MCV, were associated with successful mobilization.

Final Overall Survival, Safety, and Quality of Life Results From a Phase 2 Study of Crizotinib in East Asian Patients With ROS1-Positive Advanced NSCLC

IntroductionCrizotinib provided meaningful clinical benefit in the initial analysis of a phase 2 study in East Asian patients with advanced ROS1-positive NSCLC (NCT01945021). Nevertheless, overall survival (OS) data were immature. Here, we present the final OS, quality of life (QoL), and safety data after an additional 3 years of follow-up. MethodsIn this phase 2, open-label, single-arm trial, East Asian patients with ROS1-positive advanced NSCLC who had received less than or equal to three systemic therapies previously were treated with crizotinib 250 mg twice daily on a continuous daily dosing schedule in 28-day cycles. The OS (secondary end point) was analyzed for the total population, by country, and by number of previous chemotherapy regimens. QoL and safety were also evaluated. ResultsWith a median duration of follow-up of 56.1 months, the median OS was 44.2 months (95% confidence interval: 32.0–not reached) for the total population (N = 127). Differences in median OS were observed among individual countries and with number of previous regimens. The improvement in QoL found in the previous analysis was maintained with the extended follow-up. Treatment-related adverse events led to crizotinib dose reductions or permanent treatment discontinuations in 17.3% and 2.4%, respectively, of the patients. ConclusionsThis is the largest trial of an ALK/ROS1 inhibitor to treat patients with ROS1-positive advanced NSCLC and provides a new benchmark for OS in East Asian patients. The QoL and safety profile with long-term follow-up were consistent with previous reports and support the continued use of crizotinib in the treatment of patients with ROS1-positive advanced NSCLC.

Abstract P1-16-01: Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer: A randomized, open-label, multicenter, phase II trial (KCSG-BR15-17)

Abstract Background: Anthracyclines and taxanes are the preferred regimens for patients with advanced breast cancer and are usually introduced in earlier lines. Tumors refractory to anthracycline and taxanes are aggressive and often show rapid progression. Although single sequential chemotherapy is standard of care, combination chemotherapy is required for patients with rapid progression. Development of effective and tolerable combination regimens focused on these patients is clinically relevant. Methods: This randomized, open-label, phase II trial was conducted in 16 centers in Korea. Eligible patients were women aged 18 years or older with advanced or metastatic breast cancer previously treated with anthracycline and taxanes. A maximum of three previous chemotherapy regimens for metastatic disease were allowed. Patients were randomly assigned in a 1:1 ratio to receive vinorelbine monotherapy (25 mg/m2 days 1 and 8) or pemetrexed (500 mg/m2 day 1) plus vinorelbine (25 mg/m2 days 1 and 8) in a 21-day cycle until disease progression or unacceptable toxicity. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival, safety, and quality of life (QoL). Results: From March 2017 through August 2019, a total of 125 patients were enrolled. Sixty-two patients were assigned to pemetrexed plus vinorelbine and 63 were assigned to vinorelbine monotherapy. Baseline characteristics and demographics were well-balanced between the two treatment groups. Overall, hormone receptor was positive in 58.4% of patients and HER2 was positive in 6.4% of patients. Fifty-six percent of patients received 2 or 3 line of previous palliative chemotherapy and 41% of patients received previous endocrine therapy of palliative purpose. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine monotherapy (5.7 vs. 1.5 months, hazard ratio 0.542 [95% CI 0.374 - 0.786], p &amp;lt; 0.001). Prolonged PFS with pemetrexed plus vinorelbine compared to vinorelbine monotherapy was consistent across all patient subgroups, regardless of patient’s hormone receptor status, prior capecitabine use, prior lines of palliative chemotherapy, and metastases sites. ORR was numerically higher (15.0% vs. 9.8%) and disease control rate was significantly higher (78.3% vs. 45.9%) in patients treated with pemetrexed plus vinorelbine compared to vinorelbine monotherapy. Febrile neutropenia (16.1% vs. 4.9%, p = 0.043), liver enzyme elevation (25.8% vs. 11.5%, p = 0.042), and anemia (29.0% vs. 9.8%, p = 0.007) was more frequent in the combination arm, but the toxicities were generally manageable. There was no treatment related death and only one patient in the monotherapy arm discontinued the treatment due to febrile neutropenia. There was no difference in QoL as measured by EORTC QLC-C30 and QLQ-BR23. Conclusions: Pemetrexed plus vinorelbine led to longer progression-free survival compared to vinorelbine monotherapy with manageable toxicities. We believe pemetrexed plus vinorelbine could be considered as a treatment option in patients with advanced breast cancer. Table 1.Best tumor responseTotal (N = 123)Vinorelbine single (N = 61)Pemetrexed plus vinorelbine (N = 62)P-ValueComplete response0 (0.0%)0 (0.0%)0 (0.0%)0.001Partial response15 (12.4%)6 (9.8%)9 (15.0%)Stable disease60 (49.6%)22 (36.1%)38 (63.3%)Progressive Disease46 (38.0%)33 (54.1%)13 (21.7%) Citation Format: Dae-Won Lee, Yeon Hee Park, Kyung-Hae Jung, Kyung-Hun Lee, Keun Seok Lee, Joohyuk Sohn, Hee Kyung Ahn, Jae Ho Jeong, Su-Jin Koh, Jee Hyun Kim, Han Jo Kim, Kyoung Eun Lee, Hee-Jun Kim, Ki Hyeong Lee, Kyong Hwa Park, Jieun Lee, Hye Sung Won, Tae-Yong Kim, Seock-Ah Im. Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer: A randomized, open-label, multicenter, phase II trial (KCSG-BR15-17) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-01.

Clinical Activity and Safety of Anlotinib Combined with PD-1 Blockades for Patients with Previously Treated Small Cell Lung Cancer.

ObjectiveAnlotinib was the standard monotherapy for patients with previously treated small cell lung cancer (SCLC) in recent years. Programmed cell death protein 1 (PD-1) blockade combined with antiangiogenic targeted drugs have proved to play a synergistic action for cancer treatment clinically. Consequently, the present study was to investigate the efficacy and safety of anlotinib combined with PD-1 blockades for patients with previously treated SCLC.MethodsA total of 36 patients with SCLC who were treated with at least one previous systemic chemotherapy regimen participated in this study retrospectively. All the patients were administered with anlotinib plus PD-1 blockades therapy. Clinical activity was assessed according to the change of target lesion by imaging evidence and all the subjects were followed up regularly. Safety profiles were collected and documented during the treatment. Univariate analysis was carried out using Log rank test and multivariate analysis was adjusted by Cox regression analysis.ResultsAll the 36 patients with previously treated SCLC were able to have their efficacy and safety profile evaluated. The best overall response of the combination regimen showed that complete response was observed in one patient, partial response was noted in 9 patients, stable disease was reported in 19 patients, progressive disease was seen in 7 patients. Therefore, the objective response rate (ORR) of the 36 patients was 27.8% (95% CI: 14.2–45.2%), disease control rate (DCR) was 80.6% (95% CI: 64.0–91.8%). Regarding the prognostic data, the median PFS and OS of the 36 patients was 4.6 months (95% CI: 3.13–6.07) and 9.3 months (95% CI: 3.30–15.30), respectively. The most common treatment-related adverse reactions were hypertension (52.8%), fatigue (47.2%), diarrhea (38.9%), hand and foot reaction (38.9%) and dermal toxicity (33.3%). Furthermore, multivariate Cox regression analysis for PFS indicated that ECOG performance status was an independent factor to predict PFS.ConclusionAnlotinib combined with PD-1 blockades regimen preliminarily demonstrated encouraging efficacy and tolerable safety for patients with previously treated SCLC. The conclusion should be validated in prospective clinical trials subsequently.

Identification of Patients with Recurrent Epithelial Ovarian Cancer Who Will Benefit from More Than Three Lines of Chemotherapy.

PurposeThis study aimed to identify patients who would benefit from third and subsequent lines of chemotherapy in recurrent epithelial ovarian cancer (EOC).Materials and MethodsRecurrent EOC patients who received third, fourth, or fifth-line palliative chemotherapy were retrospectively analyzed. Patients’ survival outcomes were assessed according to chemotherapy lines. Based on the best objective response, patients were divided into good-response (stable disease or better) and poor response (progressive disease or those who died before response assessment) groups. Survival outcomes were compared between the two groups, and factors associated with chemotherapy responses were investigated.ResultsA total of 189 patients were evaluated. Ninety-four and 95 patients were identified as good and poor response group respectively, during the study period of 2008 to 2021. The poor response group showed significantly worse progression-free survival (median, 2.1 months vs. 9.7 months; p < 0.001) and overall survival (median, 5.0 months vs. 22.9 months; p < 0.001) compared with the good response group. In multivariate analysis adjusting for clinicopathologic factors, short treatment-free interval (TFI) (hazard ratio [HR], 5.557; 95% confidence interval [CI], 2.403 to 12.850), platinum-resistant EOC (HR, 2.367; 95% CI, 1.017 to 5.510), and non-serous/endometrioid histologic type (HR, 5.045; 95% CI, 1.152 to 22.088) were identified as independent risk factors for poor response. There was no difference in serious adverse events between good and poor response groups (p=0.167).ConclusionThird and subsequent lines of chemotherapy could be carefully considered for palliative purposes in recurrent EOC patients with serous or endometrioid histology, initial platinum sensitivity, and long TFIs from the previous chemotherapy regimen.