Prior Lines Of Chemotherapy Research Articles

Day -1 CD34+ Cells and Platelet Count Predict the Number of Apheresis in Poor-Mobilizer Patients Rescued by Plerixafor.

Plerixafor is widely used as up-front treatment with G-CSF to enhance peripheral blood hematopoietic stem cell output in patients failing previous mobilizations. Less frequently, plerixafor is used to rescue an unsatisfactory mobilization following chemotherapy (CT) and G-CSF. This study investigates if pre-collection factors affect the CD34+ cell harvest in chemotherapy and G-CSF mobilizations rescued by plerixafor. Clinical and hematological data relative to patients, mobilization, and apheresis products were retrospectively examined. The outcome was completing a target cell dose ≥ 2 × 106 CD34+ cells/kg at first apheresis. The effect exerted on the outcome by patient- and disease-related factors was investigated by univariate and multivariate logistic regression analysis. The analysis included data from 42 patients affected by hematological (39 patients) and non-hematological malignancies (three patients). Twenty-nine patients (69%) attained the target cell dose at first apheresis. Twelve out of the remaining 13 patients received an additional plerixafor administration, and all accomplished the transplant dose at a second apheresis procedure. Day -1 CD34+ PB count (OR1.46, 95% CI 1.1-1.9, p = 0.008) and platelet count (OR1.0, 95% CI 1.0-1.0, p = 0.033) predicted the achievement of the target dose at first apheresis, independently of pre-mobilization CT, radiation therapy, and disease status at mobilization. At ROC curve analysis, the best cut-off value predicting the successful collection at first apheresis was 7.5/µL for Day -1 CD34+ cell count (AUC 0.830, 0.69 sensitivity, and 0.92 specificity) and 75 × 109/L for Day -1 platelet count (AUC = 0.736, 0.65 sensitivity and 0.85 specificity). In conclusion, on-demand plerixafor rescue allows a successful stem cell collection, irrespectively of disease type and status, prior CT lines, and radiation exposure. Pre-apheresis CD34+ cells and platelet count predict the need for one or two aphereses.

PS-B01-9: APATINIB THROUGH ACTIVATING THE RHOA/ROCK SIGNALING PATHWAY TO CAUSE DYSFUNCTION OF VASCULAR SMOOTH MUSCLE CELLS

Apatinib is a small molecule TKI that highly selectively binds to and strongly inhibits VEGFR2. Previous studies have shown that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, hypertension is one of the main adverse effects of antiangiogenic tumour drugs and affecting the application of the drugs. Previous studies have confirmed that the RhoA/ROCK pathway is involved in the pathogenesis of hypertension. Abnormal cell proliferation and invasion of vascular smooth muscle cells are among the primary causes of cardiovascular disease. In this study, an in vitro experiment was conducted to observe whether apatinib caused dysfunction of MOVAS cells through the RhoA/ROCK signalling pathway and whether it could be improved after Y27632 intervention. Subsequently, cell lines in which the LARG gene, which is involved in the RhoA/ROCK pathway, was knocked out were constructed to observe whether LARG knockdown could improve the proliferation, antiapoptosis, oxidative stress and mitochondrial autophagy of apatinib induced MOVAS cells. To provide a basis for the prevention and treatment of this type of hypertension.

Oral paclitaxel and encequidar in patients with breast cancer: a pharmacokinetic, safety, and antitumor activity study.

Paclitaxel is widely used for the treatment of metastatic breast cancer (MBC). However, it has a low oral bioavailability due to gut extrusion caused by P-glycoprotein (P-gp). Oral paclitaxel (oPAC) may be more convenient, less resource-intensive, and more tolerable than its intravenous form. Encequidar (E) is a first-in-class, minimally absorbed, gut-specific oral P-gp inhibitor that facilitates the oral absorption of paclitaxel. To investigate the pharmacokinetics (PK), overall response rate (ORR), and safety of weekly oral paclitaxel with encequidar (oPAC + E) in patients with advanced breast cancer. This is a multicenter, single-arm, open-label study in six medical centers in Taiwan. Patients with advanced breast cancer were administered 205 mg/m2 oPAC and 12.9 mg E for 3 consecutive days weekly for up to 16 weeks. Plasma samples were collected at weeks 1 and 4. PK, ORR, and safety were evaluated. In all, 28 patients were enrolled; 27 had MBC; 23 had prior chemotherapy; and 14 had ⩾2 lines of prior chemotherapy. PK were evaluable in 25 patients. Plasma paclitaxel area under the curve (AUC)(0-52 h) at week 1 (3419 ± 1475 ng h/ml) and week 4 (3224 ± 1150 ng h/ml) were equivalent. Best overall response in 28 evaluable patients was partial response (PR) in 11 (39.3%), 13 (46.4%) stable disease (SD), and 1 (3.6%) with progressive disease (PD). No patient achieved complete response (CR). The clinical benefit rate (CR + PR + SD) was 85.7%. Major adverse events among the 28 treated patients were grade 3 neutropenia (25%), grade 4 neutropenia (18%), with febrile neutropenia in 4%, and grade 3 diarrhea (4%). No treatment-related deaths occurred. Grade 2 peripheral neuropathy occurred in 1 (4%) patient and grade 3 peripheral neuropathy in 1 (4%) patient. oPAC + E produced a consistent therapeutic plasma paclitaxel exposure during treatment. There was a high rate of radiologically assessed clinical benefit, and a low rate of neurotoxicity which may provide advantages over IV paclitaxel. ClinicalTrials.gov Identifier: NCT03165955.

The efficacy of immune checkpoint inhibitors in biliary tract cancer with KRAS mutation.

With a 15% incidence, KRAS is one of the most common mutations in biliary tract cancer (BTC) and is a poor prognostic factor. Immune checkpoint inhibitors (ICIs) as salvage therapy have modest activity in BTC. There are limited data on the efficacy of ICIs according to KRAS mutation in BTC. We evaluated the efficacy of ICIs in BTC patients with or without KRAS mutations. Retrospective observational study. We conducted molecular profiling in BTC patients who received ICIs as salvage therapy. The expression of programmed death ligand 1 (PD-L1) on tumor cells was assessed using immunohistochemistry. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. We analyzed overall survival (OS) and progression-free survival (PFS) of ICI in BTC patients according to KRAS mutation and PD-L1 expression. A total of 62 patients were included in this analysis. The median age was 68.0 years; 47 patients (75.8%) received pembrolizumab and 15 (24.2%) received nivolumab as salvage therapy. All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% received fluoropyrimidine plus oxaliplatin (FOLFOX) before ICI. The median number of lines of prior chemotherapy was 2.5. The KRAS mutation was found in 13 patients (19.1%), and 28 patients (45.2%) showed 1% or more of tumor cells out of visible tumor cells positive for PD-L1. There was no statistical correlation between KRAS mutation and PD-L1 expression. The median OS and PFS with ICI were 5.6 [interquartile range (IQR): 3.3-8.0] and 3.8 (IQR: 3.0-4.5) months, respectively. There were no statistically significant differences in PFS with ICIs according to KRAS mutation (mutant type versus wild type) and PD-L1 expression (positive versus negative). In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS compared with patients with KRAS mutation and PD-L1 negativity (10.1 versus 2.6 months, p = 0.047). This finding was not shown in patients with wild-type KRAS. Our analysis suggested that PD-L1 expression might be a useful biomarker for ICIs in BTC patients with KRAS mutation but not in those with wild-type KRAS.

Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study

PurposeTo evaluate the efficacy and safety of pamiparib in patients with locally advanced or metastatic human epidermal growth factor receptor 2-negative (HER2−) breast cancer, with deleterious or suspected deleterious germline BRCA1/2 mutations (gBRCA1/2 m).MethodsIn this open-label, phase II, multicenter study in China (NCT03575065), patients with triple-negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2− breast cancer (HR+/HER2− cohort) and ≤ 2 prior lines of chemotherapy received pamiparib 60 mg orally twice daily in 28-day, continuous cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee.ResultsIn total, 88 patients were enrolled (TNBC cohort: 62; HR+/HER2− cohort: 26). Median age was 45.5 (range: 27–67) years, and 60 patients (68.2%) had received 1 or 2 prior lines of chemotherapy; 42 patients (47.7%) had previously received platinum chemotherapy. In the TNBC cohort, ORR was 38.2% (95% confidence interval [CI] 25.4–52.3) and median duration of response (DoR) was 7.0 months (95% CI 3.9–not estimable). In the HR+/HER2− cohort, ORR was 61.9% (95% CI 38.4–81.9) and median DoR was 7.5 months (95% CI 5.6–14.8). The most common treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and ≥ Grade 3 TEAEs were hematologic (including anemia, decreased neutrophil count, and decreased white blood cell count). Overall, 64.8% of patients had TEAEs leading to dose reduction and 2.3% had TEAEs leading to treatment discontinuation.ConclusionPamiparib showed encouraging efficacy and an acceptable safety profile in patients with locally advanced and metastatic HER2− breast cancer with gBRCA1/2 m.Trial registrationClinicalTrials.gov, NCT03575065; July 2, 2018.

AlphaBet: Combination of Radium-223 and [17 7Lu]Lu-PSMA-I&T in men with metastatic castration-resistant prostate cancer (clinical trial protocol).

[177Lu]Lu-PSMA is a radioligand therapy used in metastatic castration-resistant prostate cancer (mCRPC). Despite a survival benefit, the responses for many patients receiving [177Lu]Lu-PSMA are not durable, and all patients eventually develop progressive disease. The bone marrow is the most common site of progression. Micrometastases in this area likely receive an inadequate dose of radiation, as the emitted beta-particles from 177Lu travel an average range of 0.7 mm in soft tissue, well beyond the diameter of micrometastases. Radium-223 (223Ra) is a calcium-mimetic and alpha-emitting radionuclide approved for use in men with mCRPC with bone metastases. The range of emitted alpha particles in soft tissue is much shorter (≤100 μm) with high linear energy transfer, likely more lethal for osseous micrometastases. We anticipate that combining a bone-specific alpha-emitter with [177Lu]Lu-PSMA will improve eradication of micrometastatic osseous disease, and thereby lead to higher and longer responses. This is a single-center, single-arm phase I/II trial evaluating the combination of 223Ra and [177Lu]Lu-PSMA-I&T in men with mCRPC. Thirty-six patients will receive 7.4 GBq of [177Lu]Lu-PSMA-I&T, concurrently with 223Ra in escalating doses (28 kBq/kg - 55kBq/kg), both given intravenously every six weeks for up to six cycles. Eligible patients will have at least two untreated bone metastases visible on bone scintigraphy, and PSMA-positive disease on PSMA PET scan. Patients must have adequate bone marrow and organ function and be willing to undergo tumor biopsies. Patients with discordant disease visible on FDG PET scan (defined as FDG positive disease with minimal or no PSMA expression and no uptake on bone scan) will be excluded. Other key exclusion criteria include the presence of diffuse marrow disease, prior treatment with 223Ra or [177Lu]Lu-PSMA, or more than one prior line of chemotherapy for prostate cancer. The co-primary objectives of this study are to determine the maximum tolerated dose of 223Ra when combined with [177Lu]Lu-PSMA-I&T and the 50% PSA response rate. The AlphaBet trial is a phase I/II study combining 223Ra with [177Lu]Lu-PSMA-I&T in patients with mCRPC. We aim to enroll the first patient in Q3 2022, and recruitment is anticipated to continue for 24 months. NCT05383079.

Venetoclax in Combination with Hypomethylating Agents Compared to Standard Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia

Introduction: The safety and efficacy of venetoclax (VEN) in combination with hypomethylating agents (HMA) in older adults with newly diagnosed acute myeloid leukemia (AML) or those ineligible for intensive chemotherapy is well established. Recently, VEN/HMA has emerged as a potential option in relapsed or refractory (r/r) AML. Although encouraging, data on whether this combination compares favorably to standard chemotherapy (SC) in r/r AML are limited. Methods: This was a single-center, retrospective analysis from November 2012 to March 2022 that compared VEN/HMA to SC in r/r AML patients at a 923-bed tertiary care hospital with an outpatient cancer facility. The primary endpoint was overall response rate (ORR) defined as rate of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), morphological leukemia-free state (MLFS), and partial remission (PR). Key secondary outcomes included overall survival (OS), relapse-free survival (RFS), and toxicity. Continuous variables were compared using the Mann-Whitney U test or the two-sample t-test and categorical variables were compared using the Chi-squared or Fisher's exact test. Time to event data were assessed using the Kaplan-Meier method. Log-rank test was used to compare the survival endpoints between groups. A p-value < 0.05 was considered statistically significant. Results: A total of 281 patients underwent screening, of those, 63 adult patients were included in the analysis (VEN/HMA, n = 25 and SC, n = 38). The primary reason for exclusion was previously untreated AML or myelodysplastic syndrome. Baseline characteristics were balanced between the groups. Overall, 53 patients had de novo AML, 25 patients had received 3 or more prior lines of chemotherapy, 20 patients were ≥ 60 years, and 8 patients had undergone previous stem cell transplantation. In the VEN/HMA cohort, 32% had prior exposure to a hypomethylating agent and 36% received concomitant azole antifungals. The majority of patients in both groups were stratified as intermediate or poor risk according to the European LeukemiaNet (ELN) 2017 criteria. Common chemotherapy regimens included MEC (74%), ME (12%), and FLAG ± IDA (11%). Most patients in the VEN/HMA group received decitabine and of those, 60% initiated therapy in the outpatient setting. Treatment outcomes are shown in Table 1 and OS results are presented in Figure 1. Both therapies resulted in similar ORRs (VEN/HMA 52% vs SC 42%, p=0.44). Combined CR/CRi was achieved in 36% of patients in the VEN/HMA group and 37% of patients in the SC arm (p=0.95). Median time to response was 73 days for VEN/HMA and 45 days for SC (p=0.38). The OS between VEN/HMA and SC groups was not statistically different (p=0.99, log-rank test) with median OS of 287 days and 285 days, respectively. No difference in RFS was observed between the two groups (0.38, long-rank test) with median RFS of 304 days in the VEN/HMA arm and 325 days in SC group. Prior HMA exposure in VEN-treated patients was associated with a lower CR/CRi rate (13% vs 41%, p=0.09). Induction mortality rates at 30 and 60 days were similar between the groups. Duration of hospitalization was significantly shorter in patients who received VEN/HMA as compared to those who received SC (p=0.04). In terms of safety, patients treated with VEN/HMA had lower rates of any grade diarrhea (40% vs 71%, p=0.01), any grade mucositis (20% vs 61%, p=0.001), and grade ≥ 3 anemia (80% vs 97%, p=0.02). The rate of febrile neutropenia was significantly higher in the SC group than in the VEN/HMA group (97% vs 40%, p<0.00001), as was the rate of bacterial infections (50% vs 24%, p=0.03). Fungal pneumonias were also reported more frequently in patients receiving SC (37% vs 12%, p=0.04). Lastly, a trend toward a longer median time to platelet recovery was noted in VEN/HMA patients receiving concomitant azole antifungals (38 days vs 26 days, p=0.52). Conclusion: Treatment with VEN/HMA yielded similar outcomes compared with SC and was associated with lower infection rates, a potential advantage in a patient population at high risk for infectious complications. Additionally, safe initiation of this regimen in the outpatient setting and shorter duration of hospitalization when compared to SC could lead to a reduction in use of healthcare resources and improvement in quality of life. These findings add to a growing body of evidence that suggest VEN/HMA is non-inferior to SC with a favorable toxicity profile. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clonal Myeloid Disorders Following CAR T-Cell Therapy

Background: Long-term complications of chimeric antigen receptor (CAR) T-cell therapy are not well-defined. Data on secondary malignancies after CAR T-cell therapy are emerging, and chemotherapy-related myeloid malignancies are of concern in these patients. We aimed to determine the incidence of myeloid neoplasms, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), following CAR T-cell therapy. We also aimed to determine the prevalence of somatic mutations associated with clonal myeloid disorders such as clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS) in these patients. Methods: This was a single-center retrospective cohort study that evaluated consecutive adult patients with an underlying hematologic malignancy treated with CAR T-cell therapy at our institution. We reviewed bone marrow biopsies, including cytogenetics, as well as hematologic sequencing panels following CAR T-cell therapy. Primary outcome was the cumulative incidence of myeloid neoplasms at one year. We calculated cumulative incidence with 95% confidence intervals (CI) with death as a competing event using statistical software XLSTAT. Results: A total of 78 consecutive patients who received CAR T-cell therapy between 2016 and 2022 at our institution were included. Of these, 61.5% were male and median age at time of therapy was 65.9 years (range 21.3-85.0). Patients had received a median of 3 (IQR, 2-4.1) lines of chemotherapy prior to CAR T-cell therapy, and 30.7% had undergone a prior autologous stem cell transplant. Most common indications for CAR T-cell therapy included diffuse large B-cell lymphoma (DLBCL, 57.7%) and multiple myeloma (24.4%), with the remainder split between mantle cell lymphoma (7.7%), chronic lymphocytic lymphoma (3.8%), high-grade B-cell lymphoma (2.6%), and one patient each with follicular lymphoma, follicular lymphoma transformed to DLBCL, and primary mediastinal B-cell lymphoma. Most common CAR T-cell therapies administered were lisocabtagene maraleucel (39.7%), axicabtagene ciloleucel (24.4%), and idecabtagene vicleucel (7.7%). At 30 days post-CAR T-cell therapy, 44.9% had complete response, 29.5% had partial response, 10.3% had stable disease, and 15.4% had progressive disease. A total of 37.1% died during the follow-up period; among patients who died, overall survival was a median 161 days (IQR, 104-259). Following CAR T-cell therapy, 73.1 % of patients had a bone marrow biopsy, 10.2% had a myeloid sequencing panel, and 10.3% had a lymphoid sequencing panel from peripheral blood or bone marrow. Median time of total follow-up was 14.8 months (IQR, 6.5-28.8). Two patients developed MDS and one developed AML; characteristics of patients diagnosed with a myeloid neoplasm are shown in table 1. Cumulative incidence of subsequent myeloid neoplasms at one year was 4.2% (95% CI 1.4-12.7) as shown in Figure 1. The incidence rate for development of a myeloid neoplasm was 2.3 cases per 100 person-years (95% CI, 0.60-.7.1). Additionally, four patients, including one who developed MDS, were found to have mutations associated with myeloid disorders on hematologic sequencing; this represents 5.1% of total patients and 25.0% of those with sequencing data available. Mutations are outlined in Table 1. Conclusion: A significant proportion of patients developed myeloid malignancies following CAR T-cell therapy, including two patients who had only received two lines of prior chemotherapy each. Mutations associated with myeloid neoplasms were found in one-quarter of the patients who had next generation sequencing performed. These findings suggest that further study is warranted to better define the causative role of CAR T-cell therapy in the development of myeloid disorders. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Real-World Efficacy of 5-Azacytidine as Salvage Chemotherapy for Angioimmunoblastic T-cell Lymphoma.

Based on specific epigenetic mutation in AITL such as TET2, DNMT3A, IDH2, and RHOA, hypomethylating agents are emerging as a promising treatment option for AITL. The efficacy and safety of 5-azacytidine as salvage chemotherapy were retrospectively analyzed in 15 patients with RR-AITL from 2019 to 2022. During the median 6.0 months of follow-up, the overall response rate (ORR) was 40% (n=6/15) with 2 CRs and 4 PRs. The patients who previously had received ≤2 prior chemotherapies showed higher ORR than subjects with >2 prior chemotherapies (80% vs. 20%). The 10 patients who received 5-azacitidine at the late chemotherapy lines (>2 prior chemotherapy lines) usually received less dose 5-azacitidine. And these patients discontinued treatment due to disease progression (n=6/10, 60%) or neutropenic fever (n=4/10, 40%). The patients who received a full dose (75 mg/m2 for 7 days) of 5-azacitidine seemed to show better ORR than subjects (100 mg for 7 days) who did not receive an optimal dose (60.0% vs. 30.0%). The median progression-free survival (PFS) was 1.6 months, and the patients who previously had undergone ≤2 chemotherapies had better PFS compared with subjects who previously received >2 chemotherapies (P-value=.04). 5-azacitidine shows reasonable efficacy and manageable toxicities for patients with RR-AITL, especially those who previously received ≤2 chemotherapy lines.

Safety, pharmacokinetics and efficacy of SCT200, an anti-EGFR monoclonal antibody in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer: a phase I dose-escalation and dose-expansion study

BackgroundAn over-expression of the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer and is associated with aggressive disease and poor prognosis. SCT200 is a newly developed recombinant, fully humanized, anti-EGFR monoclonal antibody. This study aimed to evaluate its safety, tolerability, pharmacokinetics (PK), and efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer (mCRC). MethodsThis phase I study comprising dose-escalation phase and dose-expansion phase. SCT200 was administrated intravenously to groups of three to six patients. An every 3-week dosing cycle (0.5–15.0 mg/kg) and multiple dosing schedule were evaluated. Blood samples were collected at preset intervals for PK assessment, radiological imaging was used for efficacy assessment, and continuous safety monitoring was performed in each group during the study. ResultsFrom December 16, 2014 to December 31, 2018, fifty-six patients with wild-type KRAS/NRAS/BRAF mCRC receiving ≥ 1 dose of SCT200 were evaluated. Among them, 44.6% (25/56) of the patients failed at least two prior lines of chemotherapy. No dose-limiting toxicities occurred in any group. All of the patients experienced treatment-emergent adverse events (TEAEs). 96.4% (54/56) of patients experienced treatment-related adverse events (TRAEs), and 26.8% (15/56) of patients with Grade ≥ 3 TRAEs. No serious TRAEs were observed. The most common TRAEs were dermotoxicity and hypomagnesemia. PK analysis showed non-linear PK in the range of 0.5 - 8.0 mg/kg of single dose SCT200, the clearance decreased, and the elimination half-life (T1/2) prolonged following dose increase. In the multiple-dose period, the clearance decreased, peak concentration increased, and T1/2 prolonged during prolonged drug administration, and a steady state was reached after five consecutive dose of 6.0 mg/kg quaque week (QW). The objective response rate (ORR) was 30.4% (17/56, 95% confidence interval [CI], 18.8%–44.1%). The ORR in the dose-expansion group (6.0 mg/kg QW) was 48.0% (12/25, 95% CI, 27.8%–68.7%), the median progression-free survival was 5.2 months (95%CI, 3.6–5.5), and the median overall survival was 20.2 months (95%CI, 12.1-not reached).ConclusionsSCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC.Trial registrationThis study was registered with ClinicalTrials.gov (NCT02211443).

Efficacy and safety of trabectedin for the treatment of advanced uterine or ovarian carcinosarcoma: Results of a phase II multicenter clinical trial (MITO-26)

ObjectiveThis open-label phase II clinical trial evaluated the antitumor activity and safety of trabectedin in patients with advanced ovarian (OC) or uterine carcinosarcomas (UC). MethodsEligible patients were adults (≥18 years) with histologically proven recurrent OC/UC not amenable to surgery or radiotherapy who received up to two prior chemotherapy lines. Trabectedin 1.3 mg/m2 was administered as a 3-h infusion every three weeks. The primary endpoint was objective response rate (ORR) as per RECIST v.1.1. If at least 8 of 43 patients (18.6%) achieve an objective response, trabectedin would be declared worthy for further investigations. ResultsForty-five patients with either OC (n = 32) or UC (n = 13) from seven MITO centers across Italy were enrolled. The ORR was 11.9% (90% CI: 6–23) and included two patients with a complete response and three with a partial response. Eight patients (19.0%) had disease stabilization for a disease control rate of 31.0% (90% CI: 20–44). Median progression-free survival was 2.01 months (95% CI: 1.78–2.30) and median overall survival was 4.64 months (95% CI: 3.19–8.29). Neutrophil count decreases (n = 8, 18.2%) and transaminase increases (n = 6, 13.6%) were the most common grade 3–5 adverse events related with trabectedin. Two patients died due to trabectedin-related grade 5 hematological toxicity. ConclusionAlthough trabectedin did not meet the prespecified activity criteria, it confers modest but clinically meaningful benefit to patients with advanced OC/UC as being as effective as any other available treatment for this indication. The toxicity profile appears in line with that previously reported for the drug.

101 (PB091) - Phase 1b results from OP-1250-001, a dose escalation and dose expansion study of OP-1250, an oral CERAN, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer (NCT04505826)

Background: OP-1250 is a small molecule oral complete estrogen receptor antagonist (CERAN) that binds the ligand binding domain of the ER and completely blocks ER driven transcriptional activity. OP-1250 potently inactivates both wild-type ER and mutant forms of ER that confer ligand independent activity and resistance to standard of care endocrine therapies. OP-1250 inhibits estrogen-driven breast cancer cell growth and induces degradation of the ER. In preclinical models, OP-1250 is active in the presence of wild-type ER, mutant ER (ESR1 activating mutations), and brain metastasis. OP-1250 is being developed for ER+, HER2- metastatic breast cancer (MBC) patients (pts). We previously reported Phase 1a (dose escalation) results, here we present data from the Phase 1b expansion portion of the clinical trial. Methods: Following Phase 1a dose escalation of OP-1250 from 30 mg to 300 mg QD, a recommended phase 2 dose (RP2D) range was defined of 60 to 120 mg QD. Sixty pts are planned for Phase 1b enrollment, with 30 pts at each dose level (60 and 120 mg). In Phase 1b eligibility included measurable disease, 1–4 prior lines of hormonal therapy, and £1 prior line of chemotherapy in the advanced setting. Pts were monitored for adverse events (AE) and tumor assessments (RECIST 1.1) were conducted every two 28-day cycles. Results: As of May 13, 2022, 37 patients were assigned to either 60 mg or 120 mg dose levels. Pts were heavily pretreated: 62% had received 2 or more prior endocrine therapies in the advanced setting, 32% received chemotherapy, and 97% had received a prior CDK 4/6 inhibitor. More than half (57%) of pts who had ctDNA evaluated had an ESR1 mutation. At 60 mg and 120 mg, OP-1250 demonstrated high oral bioavailability and dose proportional exposure. The most common treatment emergent adverse events reported (≥10%) in Phase 1b in the 60 mg/120 mg cohorts were nausea (28%/21%), vomiting (17%/16%), fatigue (17%/5%) and headache (11%/ 11%). Adverse events were Grade 1/2, with the exception of two Grade 3 events at 60 mg (diarrhea and anemia); no Grade 3 events occurred at 120 mg. There were no dose reductions or discontinuations due to an AE. Across Phase 1b, among pts eligible for at least one post-baseline scan (n = 24), 1 confirmed PR (cPR) was observed at 60 mg and 1 uPR was observed at 120 mg. Data continues to mature and updated data will be presented. Conclusions: OP-1250 was well tolerated and showed promising safety and efficacy in Phase 1b pts treated at 60 mg and 120 mg daily. Based on safety and pharmacokinetic data, a RP2D will be selected. A Phase 2 evaluation will be initiated, and a Phase 3 monotherapy study is planned for 2023. Conflict of interest: Corporate-sponsored Research: Erika Hamilton: Abbvie, Acerta Pharma, Accutar Biotechnology, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Artios, Arvinas, AstraZeneca, AtlasMedx, Black Diamond, Bliss BioPharmaceuticals, Boehringer Ingelheim, Cascadian Therapeutics, Clovis, Compugen, Cullen-Florentine, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Ellipses Pharma, Elucida Oncology, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, Infinity Pharmaceuticals, InvestisBio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millennium, Molecular Templates, Myraid Genetic Laboratories, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, Pharma Mar, Pieris Pharmaceuticals Pionyr, Immunotherapeutics, Plexxikon, Radius Health, Regeneron, Relay Therapeutics, Repertoire, Immune Medicine, Rgenix, Roche/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Tesaro, Tolmar, Torque Therapeutics, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics, Zymework Other Substantive Relationships: Erika Hamilton: Consulting Advisory Role (all to institution only): Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, Greenwich LifeSciences, H3 Biomedicine iTeosJanssen, Lilly, Loxo, Merck, Mersana, Novartis, Orum Therapeutics, Pfizer, Propella Therapeutics, Puma Biotechnology, Relay Therapeutics, Roche/Genentech, SeaGen, Silverback Therapeutics

Multicenter Real-World Data of Subsequent Chemotherapy after Progression to PARP Inhibitors in a Maintenance Relapse Setting.

Simple SummarySince the irruption of PARPi in the therapeutic armamentarium for ovarian cancer, concerns regarding post-progression treatment outcomes have emerged, owing to known crossed-resistance mechanisms between PARPi and platinum. In this multicentric retrospective series of ovarian cancer patients, we evaluated chemotherapy results upon progression to maintenance with PARPi in the relapsed setting. We further selected the population of platinum-sensitive patients (according to the classical definition) retreated with platinum (n = 74). In this platinum-sensitive population, overall response rate and survival outcomes of platinum rechallenge after PARPi were similar to historical series of the prePARPi era. However, within this group, analysis according to BRCA status showed that BRCA mutant patients (n = 35) presented higher rates of progression and worse survival outcomes under subsequent platinum than BRCA wild type patients (n = 39), with statistically significant differences. This is the largest real-world data series of ovarian cancer patients treated with platinum rechallenge in the post-PARPi scenario.Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8–17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6–9.2), and median OS (mOS) of 20.6 months (95% CI 13.6–28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2–22.2] and 10.3 [IQR 7.4–14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5–8.6) versus 7.5 months (95% CI 6.5–10.1, p = 0.03), and 16.4 (95% CI 9.3–27.5) versus 24.2 months (95% CI 17.2–NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.

217O Patient-reported outcomes (PROs) from DESTINY-Breast04, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs treatment of physician's choice (TPC) in patients (pts) with HER2-low metastatic breast cancer (MBC)

DESTINY-Breast04 (NCT03734029) showed improvement in progression-free and overall survival of T-DXd vs TPC in pts with HER2-low MBC regardless of hormone receptor status, with no new safety signals. Here we report PROs on the effect of treatment on health-related quality of life (QOL) of T-DXd vs TPC in the hormone receptor–positive cohort. Pts with centrally confirmed HER2-low (IHC1+ or IHC2+/ISH-) MBC with 1-2 prior lines of chemotherapy in the metastatic setting were assigned 2:1 to T-DXd (Q3W) or TPC (Q3W or Q4W). PROs were measured using the European Organization for Research and Treatment of Cancer QOL questionnaires (EORTC QLQ-C30, primary variable: global health status [GHS]/QOL scale score, and EORTC QLQ-BR23) and the EuroQol 5-dimension, 5-level (EQ-5D-5L) visual analog scale (VAS). PROs were assessed at prespecified timepoints per the protocol. Change from baseline (CFB) and time to definitive deterioration (TDD) were assessed. Deterioration was defined as an increase of ≥10 points. In both arms, compliance for questionnaires was >92% at baseline and >80% for cycles 2-27. Baseline GHS score was 36.3 for T-DXd and 37.8 for TPC. Mean CFB for GHS/QOL of the QLQ-C30 remained stable (within ± 10 points) over time for pts in the T-DXd arm (n=331) up to 27 cycles and TPC arm (n=163) up to 13 cycles; beyond these cycles, the number of pts on treatment (n<10%) was too low to be informative. Median TDD of QLQ-C30 GHS/QOL was 7.6 mo for T-DXd vs 5.1 mo for TPC (hazard ratio [HR], 0.71 [95% CI, 0.56-0.92]), and all prespecified QLQ-C30 subscales had longer TDD with T-DXd, including pain (HR, 0.51 [95% CI, 0.39-0.65]) and physical functioning (HR, 0.54 [95% CI, 0.42-0.70]). For breast-specific arm symptoms of the QLQ-BR23, median TDD was 9.8 mo for T-DXd vs 5.4 mo for TPC (HR, 0.67 [95% CI, 0.50-0.88]). Median TDD of EQ-5D-5L VAS was 8.8 mo for T-DXd vs 4.7 mo for TPC (HR, 0.70 [0.54-0.91]). Pts who received T-DXd maintained GHS/QOL longer than TPC in all prespecified QLQ-C30 subscales while on therapy. These results are consistent with the primary results and confirm the QOL benefit of T-DXd vs TPC for pts with HER2-low MBC.

1632P Analysis of penpulimab plus anlotinib in pleural mesothelioma or thymic carcinoma patients who have received at least one line of chemotherapy

Pleural mesothelioma and thymic carcinoma have low morbidity and few treatment options available. Penpulimab is an IgG1 PD-1 antibody, which features point mutations in the antibody Fc region to eliminate all Fc gamma receptor binding and associated effector function. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit，Preclinical research has confirmed that penpulimab and anlotinib can significantly reduce the proportion of TIM3+PD1+CD8+ T cells，improving anti-tumor efficacy. This study aimed to evaluate the efficacy and safety of anlotinib in combination with penpulimab in patients with pleural mesothelioma or thymic carcinoma who have received at least one line of chemotherapy. This study is a single-arm phase II study. Eligible patients had recurrent/metastatic pleural mesothelioma and thymic carcinoma who were inoperable or intolerant to radical radiotherapy and had failed at least first-line chemotherapy, were over 18 years old, with ECOG PS of 0-1. The primary endpoint was ORR, and secondary endpoints were DCR, PFS, DOR, OS and safety. Patients received anlotinib (12mg QD from day 1 to 14 of a 21-day cycle) plus penpulimab (200mg Q3W) until disease progression or intolerance. Between Nov 13, 2020, and May 12,2021, 12 patients were enrolled and treated, including 5 cases of thymic carcinoma and 7 cases of pleural mesothelioma. The data cutoff date was on Apr 19, 2022. There were 10 males and 2 females. All patients had ECOG PS of 1. Four patients received only one prior line of chemotherapy. 11 patients were available for tumor assessment, ORR was 18.2%, and DCR was 81.8%. The data on PFS and OS were not mature. The common TEAE were hypoalbuminemia (75%), hypertension (75%), anemia (75%), and hypertriglyceridemia(62.5%). The incidence of grade 3 or higher treatment-related AEs was 62.5%, and there was one immune-related AE of grade 3 or higher which was hypocalcemia. Penpulimab plus annlotinib demonstrated preliminary antitumor efficacy and acceptable toxicity in pleural mesothelioma or thymic carcinoma patients who have received at least one line of chemotherapy.

521MO Efficacy of pembrolizumab monotherapy (PM) for advanced clear cell gynaecological cancer (CCGC): Phase II PEACOCC trial

Advanced CCGC has poor prognosis with 2nd line objective response rates (ORR) to standard chemotherapy ranging from 0-8%. As PD-L1 expression, PD-1+ tumour infiltrating lymphocytes, pro-inflammatory cytokine signalling, high tumour mutational burden and preliminary clinical activity with PD-1 inhibitors are described in CCGC, we investigated PM for advanced CCGC. PEACOCC is a Phase II, multicentre, single arm, academic, UK trial in patients (pts) with advanced CCGC who had ≥1 prior line of chemotherapy with progression (PD) at study entry. Pembrolizumab 200mg iv q21 days was given until PD (RECIST v1.1), unacceptable adverse event (AE), 2 years (y) PM reached, patient or clinician decision. The primary endpoint was progression-free survival (PFS) rate at 12 weeks (w) (H0≤15%; H1≥33%; 5% 1-sided a; 90% power). Secondary endpoints included ORR, duration of response (DOR), PFS, overall survival (OS) and safety. From 4/3/19–20/10/21 49pts were enrolled, 48 evaluable. Median age 58.5y (32–77y), ECOG 0/1 54.2%/45.8%, 85.4% ovarian CCGC. Median prior lines systemic therapy 2 (1–6); 19pts (39.6%) had received anti-angiogenic therapy. 42pts completed median 4 cycles PM (1–25), 6pts (12.5%) continue PM. 16.7% pts had Grade (G)3 treatment-related AE (TRAE) of hyperthyroidism (n=2), acute kidney injury (AKI), raised alanine aminotransferase, raised alkaline phosphatase, anaemia, encephalitis and diabetic ketoacidosis (DKA). There were no G4 or G5 TRAE. 3pts (6.3%) discontinued PM due to TRAEs. The PFS rate at 12w was 43.8% (90%CI:31.5-56.6) exceeding the pre-stated lower bound of 15%. Best ORR was 25.0% (90%CI:15.1-37.3) [1 complete, 11 partial], with 1y DOR rate 47.7% (95%CI:14.1-75.6). After a median follow-up of 2.1y, median PFS was 12.2w (95%CI:5.9-32.9) and median OS 71.0w (95%CI:29.1-137.6). The PEACOCC trial indicates that PM is a highly effective therapy in heavily pre-treated pts with advanced CCGC: 43.8% pts were alive and progression-free at 12w. Furthermore, clinical outcomes were durable with limited toxicity. These promising results justify consideration of pembrolizumab monotherapy as a new standard-of-care for advanced CCGC.

528MO Is re-introduction or continuation of PARP inhibitors after local therapy for oligo-metastatic progression in patients with relapsed ovarian cancer relevant?

PARP inhibitors (PARPi) have revolutionized the management of High-grade epithelial ovarian cancer (HGEOC) treatment. However, a significant number of patients relapse or progress under PARPi leading to the introduction of a new line of systemic therapy as chemotherapy. In patient with a limited number of metastatic sites in progression, -referred to as the oligo metastatic progression- a potential indication for local therapy followed by re introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of local treatment on progression free survival (PFS) in these patients remains unknown. This international multicenter retrospective study evaluated the efficacy of PARPi continuation or reintroduction in patients with HGEOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and OS. 74 patients were identified in 20 centers between 04/20 and 11/21. 65% of patients were BRCA mutated and 92% had received ≥ 2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (20%), liver (11%), other visceral (9%) and other (18%). Local therapy included radiotherapy (44%), surgery (43%), both (7%), cryotherapy or radiofrequency (3%) and other (3%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After median follow up of 14.8 months, 5 patients (6.8%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]. With close to one year without progression or introduction new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi.

1420P The pharmacokinetics and the pharmacodynamic effect of ODM-208, an inhibitor of cholesterol side-chain cleavage enzyme (CYP11A1)

ODM-208 is a first-in-class, oral, non-steroidal small molecule that selectively and completely inhibits the mitochondrial cholesterol side-chain cleavage cytochrome P450 (CYP11A1) enzyme, the first and rate limiting step in steroidogenesis, leading to deficiency of endogenous steroid hormones. The pharmacokinetics (PK) of ODM-208 and the pharmacodynamics (PD) of ODM-208 by measuring serum testosterone levels were studied in the Cypides phase 1 trial in males with progressive mCRPC, who had received at least one prior line of both 2nd generation AR pathway inhibitor (ARPI) and taxane chemotherapy.

259P Efficacy of eribulin mesylate in HER2-low metastatic breast cancer (MBC): Results from three phase III studies

Breast cancer (BC) with low-level HER2 expression (HER2-low) is defined by an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification or excess gene copy number as measured by in situ hybridization (ISH). HER2-low BC may respond differently to treatment than BC with no HER2 expression (HER2-0); thus, we conducted an unplanned post hoc analysis of three randomized, pivotal phase III studies (Studies 301, 304, and 305) to compare eribulin vs other chemotherapies in patients (pts) who had MBC. Pts enrolled had MBC and ≤2 (Study 301) or 2-5 (Studies 304, 305) prior lines of chemotherapy for advanced/recurrent/metastatic disease including an anthracycline and a taxane. Pts were treated with eribulin vs capecitabine (Study 301), vinorelbine (Study 304), or treatment of physician’s choice (TPC; Study 305). Median OS, median PFS, and ORR were analyzed, the latter two per RECIST (Studies 301, 305: v1.0; Study 304: v1.1) by independent imaging review. ORR was measured in the intent-to-treat population (Studies 301, 304) and in evaluable pts (Study 305). Eligible enrolled pts are shown in the Table; baseline characteristics were generally balanced between treatment arms in all studies; all pts in Study 304 were Chinese. PFS and OS outcomes were generally similar or improved with eribulin vs chemotherapy in pts with HER2-low and HER2-0 MBC, irrespective of study (Table); PFS and OS were generally similar among HER2-low, HER2-0, and HER2-positive pts randomized to eribulin. ORR for eribulin vs capecitabine was similar in Study 301 for HER2-low (8.8% vs 10.4%) and HER2-0 pts (10.1% vs 8.9%). ORR generally trended towards improvement with eribulin vs vinorelbine in Study 304 (HER2-low: 34.8% vs 22.4%; HER2-0: 24.5% vs 18.0%) and eribulin vs TPC in Study 305 (HER2-low: 18.8% vs 6.1%; HER2-0: 10.4% vs 4.0%).Table: 259PHER2Low0nOSaPFSanOSaPFSa301Eribulin11415.7; 13.1-18.14.1; 2.8-5.424815.9; 14.6-18.64.0; 3.0-4.3Capecitabine13513.5; 10.3-15.93.6; 2.7-4.223713.5; 11.8-15.54.0; 3.0-4.9HR0.91.00.81.195% CI0.7-1.20.7-1.40.6-<1.00.9-1.3304Eribulin6913.2; 11.4-21.14.1; 2.8-4.210213.5; 9.3-17.62.8; 2.7-4.1Vinorelbine6711.0; 9.9-16.93.2; 2.7-4.210014.3; 10.6-NE2.7; 1.4-2.8HR0.90.91.10.795% CI0.5-1.40.6-1.30.8-1.70.5-0.9305Eribulin12112.8; 9.1-15.73.7; 3.1-4.122213.8; 12.0-14.93.7; 3.1-4.9TPC5711.0; 7.7-NE2.1; 1.9-3.711710.2; 8.4-14.62.2; 1.9-3.3HR0.80.70.80.795% CI0.5-1.30.4-1.00.6-1.10.6-<1.0aUnits: mo; 95% CI. HR, hazard ratio; NE, not estimable. Open table in a new tab aUnits: mo; 95% CI. HR, hazard ratio; NE, not estimable. Eribulin had efficacy regardless of HER2 status, and, in HER2-low pts, had similar or numerically superior outcomes vs chemotherapy in each study..