Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates.

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.

Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study.

BACKGROUND: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. METHODS: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. RESULTS: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12-23 months, 18/43 (42%); 24-35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12-23 months, 0/19 (0%); 24-35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. CONCLUSIONS: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

Successful osimertinib rechallenge without concomitant corticosteroids after osimertinib-induced pneumonitis.

A 60-year-old woman was diagnosed with cT4N3M1c stage IVB lung adenocarcinoma with epidermal growth factor receptor mutation of exon19 deletion. After one month of treatment with osimertinib, a cough and diffuse ground glass opacities were observed in the bilateral lung field. Based on the clinical course and the exclusion of other etiologies, osimertinib-induced pneumonitis was diagnosed. The shadows resolved after osimertinib was discontinued. However, brain metastasis and leptomeningeal metastasis developed 20 months later; therefore, osimertinib was re-administered without concomitant corticosteroids. The pulmonary lesion and leptomeningeal metastasis were successfully treated without recurrence of drug-induced pneumonitis for eight months.

B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.

Adeno-associated virus (AAV) vectors are used for correcting multiple genetic disorders. Although the goal is to achieve lifelong correction with a single vector administration, the ability to redose would enable the extension of therapy in cases in which initial gene transfer is insufficient to achieve a lasting cure, episomal vector forms are lost in growing organs of pediatric patients, or transgene expression is diminished over time. However, AAV typically induces potent and long-lasting neutralizing antibodies (NAbs) against capsid that prevents re-administration. To prevent NAb formation in hepatic AAV8 gene transfer, we developed a transient B cell-targeting protocol using a combination of monoclonal Ab therapy against CD20 (for B cell depletion) and BAFF (to slow B cell repopulation). Initiation of immunosuppression before (rather than at the time of) vector administration and prolonged anti-BAFF treatment prevented immune responses against the transgene product and abrogated prolonged IgM formation. As a result, vector re-administration after immune reconstitution was highly effective. Interestingly, re-administration before the immune system had fully recovered achieved further elevated levels of transgene expression. Finally, this immunosuppression protocol reduced Ig-mediated AAV uptake by immune cell types with implications to reduce the risk of immunotoxicities in human gene therapy with AAV.

Efficacy and safety of streptozocin-based chemotherapy for gastroenteropancreatic neuroendocrine tumors in Japanese clinical practice.

BACKGROUND: Streptozocin has been used to treat neuroendocrine tumors in Europe and the USA; however, its actual status in Japan has not been fully clarified owing to the rarity of this disease and the relatively recent approval of streptozocin in Japan. METHODS: We retrospectively analyzed 53 patients with gastroenteropancreatic neuroendocrine tumors who were treated with streptozocin-based chemotherapy at two Japanese hospitals between January 2004 and June 2023. RESULTS: The overall response and disease control rates were 27.7 and 74.5%, respectively, and the median progression-free survival and overall survival were 7.1 and 20.3 months, respectively. Performance status ≥1 showed a significant negative correlation with progression-free survival, and performance status ≥1 and liver tumor burden ≥25% showed a significant negative correlation with overall survival. No significant differences were observed in the treatment response between pancreatic and gastrointestinal neuroendocrine tumors. No treatment-related serious adverse events were observed; however, 87.7% of patients expressed a decrease in the estimated glomerular filtration rate, which negatively correlated with the duration of streptozocin treatment (r = 0.43, P = 0.0020). In the streptozocin re-administration group (n = 5), no differences were found in efficacy between the initial and second streptozocin treatments. CONCLUSIONS: Although streptozocin is a safe, streptozocin-induced renal dysfunction is a dilemma in streptozocin responders. Streptozocin may benefit patients with gastroenteropancreatic neuroendocrine tumors, especially those with a good performance status; however, in some cases, planned streptozocin withdrawal or switching to other drugs should be considered.

Intravenous Iron Therapy: Re-administration after Prior Adverse Reaction.

BACKGROUND: Intravenous (IV) iron therapy is performed in community practices and hospitals with modern formulations when oral administration becomes impractical. Effective replacement of iron is important for the treatment of iron deficiency and anemia. Can IV iron be rechallenged in individuals with a history of adverse reactions? This review is to explore the challenge of this, when clinically indicated. METHODS: After performing a literature search, five studies (combined total sample number=1,006) for re-exposure of IV iron to individuals with a history of past reactions were identified, observed, and analyzed. Re-exposure included reactions ranging from mild to moderate and few cases of severe type. RESULTS: The majority (>80%) of IV iron rechallenges were tolerable, safe, and successful without major serious incidents. There were no reports of major reactions (severe hypersensitivity reactions or anaphylaxis) in these re-exposures. CONCLUSION: Re-administration of IV iron therapy in patients with a previous adverse reaction is plausible, with benefit and risk stratification. A rechallenge would depend on the nature and degree of the adverse reaction and use of alternative formulations. Rechallenge to a previous severe hypersensitivity reaction or anaphylaxis with the same product has not been reported in these studies. Evidence on the benefit of premedication use is conflicting and requires further studies.

Successful liver transduction by re-administration of different adeno-associated virus vector serotypes in mice.

BACKGROUND: Intravenous administration of adeno-associated virus (AAV) vectors is a promising gene therapy approach for monogenic diseases. However, re-administration of the same AAV serotype is impossible because of the induction of anti-AAV neutralizing antibodies (NAbs). Here, we examined the feasibility of re-administrating AAV vector serotypes different from the initial AAV vector serotype. METHODS: Liver-targeting AAV3B, AAV5, and AAV8 vectors were intravenously injected in C57BL/6 mice, and the emergence of NAbs and the transduction efficacy following re-administration were evaluated. RESULTS: For all serotypes, re-administration of the same serotype was not possible. Although the highest neutralizing activity of NAb was induced by AAV5, anti-AAV5 NAbs did not react with other serotypes, resulting in successful re-administration with the other serotypes. AAV5 re-administration was also successful in all mice treated with AAV3B and AAV8. Effective secondary administration of AAV3B and AAV8 was observed in most mice initially administrated AAV8 and AAV3B, respectively. However, few mice developed NAbs cross-reacting with the other serotypes, especially those with close sequence homology. CONCLUSIONS: In summary, AAV vector administration induced NAbs relatively specific to the administrated serotype. Secondary administration of AAVs targeting liver transduction could be successfully achieved by switching AAV serotypes in mice.

Survey of Anaphylaxis during Rasburicase Re-Administration in Patients with Hematological Malignancies Using a Japanese Claims Database.

Management of tumor lysis syndrome (TLS) associated with cancer chemotherapy for malignant tumors is important because of its potentially fatal course. The use of rasburicase, a recombinant urate oxidase, is recommended for TLS; however, because rasburicase is an enzymatic drug, one should be cautious of anaphylaxis during administration. Using claims data in Japan, we investigated the rate of rasburicase re-administration and the occurrence of anaphylaxis during re-administration in patients with hematopoietic malignancies in a multicenter setting. Re-administration of rasburicase was defined as administration after an interval of 21 days from the first dose. Of 373 patients, 18 were re-administered rasburicase (re-administration rate: 4.8%). No patient developed anaphylaxis. The median number of days from the first to the last dose of rasburicase was 256.5 days (interquartile range: 138.8-455.8 days). The median daily dose was 7.5 mg (4.5-11.3 mg), and the median total dose was 33.8 mg (19.1-64.1 mg). This claims database analysis revealed that the re-administration rate of rasburicase was low in Japanese patients with hematopoietic malignancies, suggesting that rasburicase was being used appropriately, and that associated anaphylaxis was not observed.

EGFR-TKI re-administration after osimertinib failure in T790M mutation loss cases with re-biopsy.

Data on the re-administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) after osimertinib failure in patients with T790M-positive non-small cell lung cancer (NSCLC) is limited. EGFR-TKI re-administration efficacy may vary between patients with T790M loss and those with T790M persistent with re-biopsy after osimertinib treatment. Patients who received EGFR-TKI re-administration (gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) after osimertinib failure were identified from our database. T790M mutation status before EGFR-TKI re-administration was analyzed via repeat biopsy. We retrospectively evaluated the efficacy of EGFR-TKI re-administration, especially differences according to the T790M mutation status, via repeat biopsy. Until June 2020, 28 patients received EGFR-TKI re-administration and 17 underwent repeat biopsy after osimertinib failure. Patients were divided into three groups, including the T790M loss group, where active mutation persisted and T790M was lost (13/17); T790M remaining group, where both the active mutation and T790M persisted (3/17); and active mutation loss group where both the active mutation and T790M were lost (1/17). The overall response rate (ORR) of EGFR-TKI re-administration in the T790M loss group was 31% and the disease control rate (DCR) was 54%, which were higher than the ORR of 21% and DCR of 43% in the entire patient population. ORR and DCR of the not re-biopsy group were low (9% and 27%, respectively). The therapeutic effect of EGFR-TKI re-administration in patients with T790M-positive NSCLC after osimertinib failure is limited. EGFR-TKI re-administration may be considered in cases of T790M loss after repeat biopsy.

Multiple Phenotypic Conversion in Malignant Melanoma: Obtainment of Granulocyte Colony-Stimulating Factor-Producing Ability during the Intermission of Nivolumab Therapy.

Malignant melanoma (MM) is one of the most aggressive, recalcitrant, and recurrence-prone skin neoplasms. Its feature is likely to be associated with phenotypic conversion due to tumor heterogeneity. The multidisciplinary assessment, including surgery, drug therapy using anticancer agents and immune checkpoint inhibitors, and radiotherapy, is needed for the treatment of advanced MM. Herein, we report a long-term follow-up MM, in which multiple phenotypic conversion occurred during several treatments. In particular, our case obtained granulocyte colony-stimulating factor-producing ability during the intermission of nivolumab therapy and it was successfully controlled by re-administration of nivolumab. Sharing the case having a varied clinical course is meaningful to increase the knowledge and decision branches for the treatment of melanoma.

An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer.

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.

For which lung cancer patients is re-administration of immune checkpoint inhibitors effective?

Objective: Currently, immune checkpoint inhibitors (ICIs) play a central role in the treatment of lung cancer. However, ICI re-administration is still uncommon, and its utility should be evaluated as early as possible. Patients and Methods: Twenty-five patients who received ICIs twice or more in any of the drug treatment lines for advanced/relapsed non-small cell lung cancer were included. OS, PFS, ORR, and DCR were examined, and factors such as age, sex, histopathological type, PD-L1 expression, whether radical surgery was performed, driver gene mutations, and immune-related adverse events (irAEs), were evaluated for their relevance and as prognostic factors. Results: Of the 25 patients, 17 were men and 8 were women, with an average age of 68 ± 8.4 (range, 48-85 years), and histology was non-squamous cell carcinoma/squamous cell carcinoma in 19/6 cases. One driver gene mutation positive case was included. PD-L1 TPS was ≥50%/1-49%/0-1%/ unknown in 7/8/5/5 cases. The first ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/13/7 cases. The median number of courses was 9 (range, 1-52) months, and the median PFS was 9 (95% CI, 6.0-12.0) months. Cytotoxic chemotherapy or radiation therapy was administered to 6 patients during the interval up to re-administration. The second ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/8/12 cases, and all patients received antibody drugs different from those given as the first ICI. The median number of courses was 5 (range, 1-24), and the median PFS was 3 months (95% CI, 1.0-5.0) months. In 5 of the 6 patients (24%) who achieved PFS of 6 months or longer after re-administration, the order of administration was anti-PD-1 antibody to anti-PD-L1 antibody. Conclusion: The effect of re-administration is limited, but it may be effective depending on the type of cases and the order of ICI administration. Further studies are required to verify its effectiveness.

Effectiveness and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced Non-Small-Cell Lung Cancer Harboring Drug-Sensitive EGFR Mutations.

Background and Objectives: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective first-line chemotherapeutic agents for patients with advanced non-small-cell lung cancer (NSCLC) harboring drug-sensitive EGFR mutations. However, the effectiveness of EGFR-TKI rechallenge after first-line EGFR-TKI treatment is not sufficient in elderly patients (over 75 years of age) harboring drug-sensitive EGFR mutations. Therefore, we investigated the effectiveness and safety of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations. Materials and Methods: Between April 2008 and December 2015, we analyzed 78 elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations with first-line EGFR-TKI treatment at four Japanese institutions. We retrospectively evaluated the clinical effectiveness and safety profiles of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Results: Twenty-two patients in the cohort were rechallenged with EGFR-TKI. The median age was 79.5 years (range 75-87 years). Despite the fact that it was a retrospective analysis, even with EGFR-TKI rechallenge treatment the response rate was 23%, progression-free survival was 5.3 months, and overall survival was 14.4 months. Common adverse events included rash acneiform, paronychia, diarrhea, and anorexia. There were no treatment-related deaths. Due to the occurrence of adverse events of grade 2 or more, dose reduction was performed in 15 (68.2%) of 22 cases. Conclusions: EGFR-TKI rechallenge treatment after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations was one of the limited, safe and effective treatment options for elderly EGFR-positive lung cancer patients.

A novel osimertinib-resistant human lung adenocarcinoma cell line harbouring mutant EGFR and activated IGF1R.

OBJECTIVE: A third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is the standard treatment for patients with non-small cell lung cancer harbouring mutant EGFR. Unfortunately, these patients inevitably acquire resistance to EGFR-TKI therapies, including osimertinib. However, the mechanism associated with this resistance remains unclear. METHODS: A 63-year-old Japanese female with lung adenocarcinoma underwent right upper lobectomy (pT1bN2M0 pStage IIIA, EGFR Ex21 L858R). She manifested post-operative tumour recurrence with multiple lung metastases 8 months later and began gefitinib treatment. The lung lesions re-grew 15 months later, and EGFR T790M mutation was detected in the lung metastasis re-biopsy. She was administered osimertinib; however, it relapsed with pleural effusion 16 months later. We isolated cells from the osimertinib-resistant pleural effusion to establish a novel cell line, ABC-31. RESULTS: Although the EGFR L858R mutation was detected in ABC-31 cells, the T790M mutation was lost. ABC-31 cells were resistant to EGFR-TKIs, including osimertinib. Phospho-receptor tyrosine kinase array revealed activation of the insulin-like growth factor 1 receptor (IGF1R), whereas overexpression of the IGF1R ligand, IGF2, induced IGF1R activation in ABC-31 cells. Combination therapy using EGFR-TKIs and IGF1R inhibitor acted synergistically in vitro. She was re-administered osimertinib since EGFR-TKIs and IGF1R inhibitor combination therapy was impossible in clinical practice. This had a slight and short-lived effect. CONCLUSIONS: Taken together, we have successfully established a new osimertinib-resistant lung adenocarcinoma cell line with activated IGF1R. These ABC-31 cells will help develop novel therapeutic strategies for patients with lung adenocarcinoma resistant to specific treatment via IGF1R activation.

Dacomitinib as a retreatment for advanced non-small cell lung cancer patient with an uncommon EGFR mutation.

In non-small cell lung cancer (NSCLC), uncommon epidermal growth factor receptor (EGFR) mutations are mutations other than Ex19 deletion and Ex21 L858R, which are common mutations highly sensitive to EGFR-tyrosine kinase inhibitors. Afatinib, a second-generation EGFR-tyrosine kinase inhibitor, has been shown to be effective in patients with uncommon mutations. Dacomitinib, another second-generation EGFR-tyrosine kinase inhibitor, has not previously been shown to be effective in patients with uncommon mutations. Here, we report the efficacy of dacomitinib for uncommon EGFR mutations in a 71-year-old woman diagnosed with metastatic lung adenocarcinoma with uncommon EGFR mutation (Ex18 G719A). Afatinib was administered as the first-line treatment, and a remarkable antitumor effect was observed. However, the tumor grew after 14 months. Pemetrexed plus carboplatin followed by pemetrexed, docetaxel, atezolizumab and S-1 were performed in sequence. Although approximately four years had passed since the start of treatment, her physical condition was good. The patient started dacomitinib as the sixth-line treatment. Lesions were markedly reduced and treatment with dacomitinib was continued for 7.8 months. Dacomitinib is a possible treatment option for NSCLC with uncommon mutations.

For which lung cancer patients is re-administration of immune checkpoint inhibitors effective? / Journal of Rural Medicine

Objective: Currently, immune checkpoint inhibitors (ICIs) play a central role in the treatment of lung cancer. However, ICI re-administration is still uncommon, and its utility should be evaluated as early as possible.Patients and Methods: Twenty-five patients who received ICIs twice or more in any of the drug treatment lines for advanced/relapsed non-small cell lung cancer were included. OS, PFS, ORR, and DCR were examined, and factors such as age, sex, histopathological type, PD-L1 expression, whether radical surgery was performed, driver gene mutations, and immune-related adverse events (irAEs), were evaluated for their relevance and as prognostic factors.Results: Of the 25 patients, 17 were men and 8 were women, with an average age of 68 ± 8.4 (range, 48–85 years), and histology was non-squamous cell carcinoma/squamous cell carcinoma in 19/6 cases. One driver gene mutation positive case was included. PD-L1 TPS was ≥50%/1–49%/0–1%/ unknown in 7/8/5/5 cases. The first ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/13/7 cases. The median number of courses was 9 (range, 1–52) months, and the median PFS was 9 (95% CI, 6.0–12.0) months. Cytotoxic chemotherapy or radiation therapy was administered to 6 patients during the interval up to re-administration. The second ICI administered was pembrolizumab/nivolumab/atezolizumab in 5/8/12 cases, and all patients received antibody drugs different from those given as the first ICI. The median number of courses was 5 (range, 1–24), and the median PFS was 3 months (95% CI, 1.0–5.0) months. In 5 of the 6 patients (24%) who achieved PFS of 6 months or longer after re-administration, the order of administration was anti-PD-1 antibody to anti-PD-L1 antibody.Conclusion: The effect of re-administration is limited, but it may be effective depending on the type of cases and the order of ICI administration. Further studies are required to verify its effectiveness.

Safe Coated Microneedles with Reduced Puncture Occurrence after Administration.

The goal of this study is the preparation of safer coated microneedles so that tips remaining after the initial use are less likely to be reinserted on a second use. Twelve groups of uncoated microneedles (u-MNs) were prepared from the combination of three different aspect ratios (height to base width) and four kinds of polymer (polyethylene (PE), polypropylene (PP), nylon and polylactic acid (PLA)). After coating the u-MNs with polyvinyl alcohol formulation to make coated MNs (c-MNs), the force displacement of the u-MNs and the c-MNs was measured. The aspect ratio was reduced from 2.2, 2.5 and 3.0 with u-MNs to 1.3, 1.4 and 1.6 with c-MNs, respectively, after the coating formulation was applied to the MNs. All PLA MNs had a puncture performance of more than 95%. However, the puncture performance of u-MNs made of PE and of PP with a 3.0 aspect ratio was only 8% and 53%, respectively, whereas the rates of c-MNs made of PE and of PP were 82% and 95%, respectively. In animal experiments with PP MNs with a 3.0 aspect ratio, the 59% rate of puncture performance with u-MNs increased to above 96% with c-MNs and fell to 13% for r-MNs. Safe c-MNs can overcome the disadvantages of standard c-MNs by reducing the probable contamination of remaining tips after use. Safe c-MNs have advantages over standard c-MNs in terms of humidity resistance, reasonable cost, sterilization process and short processing time through the separate process of u-MN preparation and simple dip-coating.

A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience.

PURPOSE: Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement. METHODS: HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed. RESULTS: A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/µL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/µL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers. CONCLUSION: In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.