Oral Vinorelbine Research Articles

Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC). NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared. Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6months (95% CI 4.8 to 6.4months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3months (95% CI 0.1 to 12.5months) and DCR of 86.7%. Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.

Efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine in elderly pre-treated patients with metastatic non-small-cell lung cancer.

e20556 Background: The subsequent therapy of elderly non-small cell lung cancer (NSCLC) without driver oncogene has always been a challenge due to the poor performance status and multiple comorbidities, especially in those who acquired resistance to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time which shows a better safety profile, antitumor angiogenesis, and immune modulatory effects compared with traditional chemotherapy. Here we designed an observational study to evaluate the efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine(mOV) in elderly pre-treated metastatic NSCLC. Methods: Patients aged 65 years and above who had been histologically or cytologically confirmed unresectable stage III and IV NSCLC were recruited for this study. All the pts had no EGFR mutation, ALK fusions, or ROS1 fusions and received at least one systematic treatment. Pts received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) for 6 cycles, followed by PD-1 inhibitors maintenance until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: From May 2020 to June 2023, 23 pts were enrolled in the study. The median age was 70 with 18(78%) males. Median follow-up time was 22.8 months (range 3.9months-41.9months). The median PFS was 5.13 months (95%Cl: 3.1 months-7.1 months) and the median OS was 28.1 months (95%Cl: (15.2 months-NA). The ORR and DCR were 13% (95%C1: 1.44%-27.6%) and 69.6% (95%Cl: 49.2%-89.9%), respectively. The PFS (p = 0.459, HR = 0.671 95%CI 0.233-1.932) and OS (p = 0.483, HR = 1.607 95%CI 0.426-6.056) were similar between those pts who previously received immunotherapy (N = 16, 69.5%) and not. PD-L1 TPS didn’t affect the patient’s PFS (&lt;1% vs≥1%, p = 0.078, HR = 2.648 95%CI 0.895-7.835 ) and OS(&lt;1% vs≥1%, p = 0.306, HR = 2.202 95%CI 0.485-9.989). Adverse events (AEs) of any grade were observed in 20(86.9%) pts of which grade III-IV AEs occurred in 4 (17.4%) pts. These grade III-IV events consisted of interstitial pneumonia, pulmonary infection, leukopenia, and neutropenia. Immune-related adverse events (irAEs) occurred in 4 (17.4%) pts, of which grade III irAEs occurred in 2 (8.7%) patients with interstitial pneumonia. No grade 4 irAEs and grade 5 adverse events even occurred. Conclusions: The regimen of PD-1 inhibitors plus mOV for the subsequent therapy showed good overall survival benefits and safety in elderly patients with metastatic NSCLC without driver oncogene which suggests it is worth further exploration.

Abstract PO1-04-04: Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial

Abstract Aim: The efficacy and safety of inetetamab in combination with pyrotinib and oral vinorelbine was investigated in patients with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. Methods: In this prospective, single-arm, phase 2 trial, patients with HER2-positive metastatic breast cancer after progression on trastuzumab were recruited. Patients received combined treatment of inetetamab (loading dose of 8 mg/kg, subsequent doses 6 mg/kg, intravenously once every 3 weeks) plus pyrotinib (400 mg orally once daily) plus vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR) and safety. The study was retrospectively registered in ClinicalTrials.gov on March 23rd, 2023. The registration number is NCT05823623. Results: Between Jan 1, 2022, and Dec 31, 2022, thirty patients were screened and enrolled to this study. The patients’ median age at enrollment was 54 years, twelve patients (40.0%) had hormone receptor-positive disease and 23 patients (76.7%) had visceral metastasis. The median PFS was 8.63 months (95% confidence interval [CI] 4.15 to 13.12 months). ORR was 53.3% (16/30) and DCR reached 96.7% (29/30). The most common grade III/IV adverse events included leukopenia (5[16.7%]), neutropenia (4[13.3%]) and diarrhea (3[10%]). No treatment-related serious adverse events or treatment-related deaths occurred. Conclusions: The combination regimen of inetetamab plus pyrotinib plus oral vinorelbine showed an encouraging efficacy and favorable safety in patients with HER2 positive metastatic breast cancer. Citation Format: Xiang Huang, Nan Jin, Chunxiao Sun, Xueqi Yan, Fan Yang, Yan Liang, Wei Li, Yongmei Yin. Inetetamab combined with pyrotinib and oral vinorelbine for patients with HER2-positive metastatic breast cancer: a single-arm phase 2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-04.

The efficiency and safety of low-dose apatinib combined with oral vinorelbine in pretreated HER2-negative metastatic breast cancer.

Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

Single-agent metronomic versus weekly oral vinorelbine as first-line chemotherapy in patients with HR-positive/HER2-negative advanced breast cancer: The randomized Tempo Breast study

IntroductionSingle-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. MethodsIn this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). ResultsOne-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0–73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8–82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. ConclusionsIn this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. Clinical trial registration numberEudraCT 2014-003860-19.

David Slays Goliath: Exceptional Efficacy of Oral Vinorelbine in Conquering Metastatic Finger Angiosarcoma

Abstract Angiosarcoma (AS) is a rare and aggressive disease originating from blood or lymphatic vessel endothelium, representing &lt;1% of soft-tissue sarcomas. The prognosis is generally poor, with a 5-year survival rate of only 30%–50%. The recurrence rate is high, and metastasis occurs in about half of the cases. The National Comprehensive Cancer Network guidelines recommend anthracycline-based, gemcitabine-based, and paclitaxel regimens as preferred first-line treatments for metastatic AS. Vinorelbine, a vinca alkaloid, is listed as supportive care in AS for patients unsuitable for intensive chemotherapy or who are heavily treated. Although the efficacy of vinorelbine is modest, some studies suggest its synergistic effect with immunotherapy. In our case report, a patient with metastatic AS received frontline paclitaxel followed by pembrolizumab, but this treatment failed. However, a complete response (CR) was achieved after oral vinorelbine. Remarkably, the patient remains in CR for 4.5 years after discontinuing vinorelbine.

Efficacy of Osimertinib Continuation Plus Metronomic Oral Vinorelbine for EGFRmutant Advanced NSCLC Beyond Limited Progression on Osimertinib.

Treatment options for advanced non-small-cell lung cancer (NSCLC) after osimertinib failure are limited, and osimertinib continuation is recommended for selected patients. Metronomic oral vinorelbine is an effective treatment with less toxicity for advanced NSCLC. The objective of the study was to investigate the effects of osimertinib plus metronomic oral vinorelbine on epidermal growth factor receptor (EGFR)-mutant advanced NSCLC beyond limited progression on osimertinib. We have reviewed the medical records of 28 patients with EGFR-mutant advanced NSCLC who had received osimertinib continuation plus metronomic oral vinorelbine beyond limited progression on osimertinib. We also evaluated the clinicopathological characteristics of enrolled patients, as well as the efficacy and toxicity of the treatment. After a median follow-up period of 14.1 months, 57.1% (16/28) of cases showed NSCLC progression. The median progression-free survival (PFS) period under osimertinib plus metronomic oral vinorelbine was 9.4 months (95% confidence interval, 1.562-17.238 months), with a disease control rate of 89.3% and objective response rate of 17.9%. PFS did not differ between patients who had previously received osimertinib as first- (n = 16) and second-line (n = 12) therapy (median, 11.4 and 4.7 months, P = 0.391). In addition, the median PFS duration did not differ according to the efficacy (PFS2 ≥ 6 months vs. <6 months) of previous osimertinib monotherapy (median, 5.8 and 9.4 months, P = 0.677). Osimertinib continuation in conjunction with metronomic oral vinorelbine may enable overcoming TKI resistance and prolong the survival of patients with EGFR-mutant advanced NSCLC beyond limited progression on osimertinib treatment.

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial

BackgroundHuman epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment. MethodsIn this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m2 orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety. ResultsBetween February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15–13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred. ConclusionsThe combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients. Trial registrationNo.NCT05823623; https://www.clinicaltrials.gov/.

Preliminary efficacy and safety of camrelizumab plus metronomic oral vinorelbine as first-line therapy for people aged 70 and above with advanced non-small cell lung cancer (NSCLC) from a phase II trial.

e14677 Background: Traditional platinum-based combination chemotherapy used as the standard first‐line treatment for advanced NSCLC poses potential safety risk for patients (pts) aged 70 years and above. Moreover, data on immune checkpoint inhibitors treating older pts with lung cancer in the current pivotal trials is limited. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time. Compared with traditional chemotherapy, MCT shows better safety profile and antitumor angiogenesis and immunomodulatory effects. Camrelizumab, an anti-PD-1 inhibitor, demonstrated encouraging efficacy in NSCLC (CameL study and CameL-sq study). Here, we designed a phase II trial to evaluate the efficacy and safety of camrelizumab plus metronomic oral vinorelbine (mOV) as first-line therapy for Chinese older pts with advanced NSCLC. Methods: Key inclusion factors were pts aged 70 years and above, histologically or cytologically confirmed unresectable stage III and IV NSCLC without positive EGFR mutation, ALK fusions or ROS1 fusions, ECOG performance status 0-2, no previous systematic treatment. Pts received camrelizumab (200mg, D1, q3w) combined with mOV (30mg, tiw1, day 1-3-5 per week) for 6 cycles, followed by camrelizumab monotherapy maintenance until disease progression or intolerable side effects. The primary endpoint was progression free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Results: From March 2021 to November 2022, 12 pts were evaluable for inclusion in the study. The median age was 77 (range: 70-85) with 8 (67%) males. Median follow-up was 7.2 months (range 2.8 months-22.1 months). The median PFS was 9.3 months (95%CI: 3.9 months-14.7 months). The one-year OS rate was 66.3%. The ORR and DCR were 50% (95%CI: 25.4%-74.6%) and 83.3% (95%CI: 50.9%-90.1%), respectively. Pts with positive or negative PD-L1 responded similarly to the treatment (respectively at 5/8 and 1/2 on ORR). The median OS and DoR have not been reached. Adverse events (AEs) with any grade were observed in 10 (83.3%) pts, of which grade III-IV AEs were observed in 2 (16.7%) pts with neutropenia and interstitial pneumonia, respectively. Immune-related adverse events (irAEs) occurred in 3 (25%) pts, of which grade III-IV irAEs occurred in one (8.3%) patient with interstitial pneumonia. No grade 5 adverse event happened. Conclusions: The regimen of camrelizumab plus mOV for the first-line therapy for older NSCLC pts showed initial promising efficacy and safety profile, which suggests it is worth further exploration. Clinical trial information: ChiCTR2100049487 .

Combined chemo-endocrine therapy as a potential new option for HR+/HER2- advanced breast cancer: a prospective study of fulvestrant plus oral vinorelbine.

Endocrine therapy with fulvestrant has shown synergistic antitumor effects with some chemotherapy drugs in vitro. This study evaluated the efficacy and safety of fulvestrant with vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) recurrent or metastatic breast cancer. Patients were intramuscularly administered fulvestrant 500 mg (day 1 per cycle for 28 days) and oral vinorelbine (60 mg/m2 on days 1, 8, and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, objective response rate, disease control rate, duration of response, and safety. A total of 38 patients with HR+/HER2- advanced breast cancer included in the study were followed up for a median time of 25.1 months. The overall median PFS was 9.86 months [95% confidence interval (CI) 7.2-23.13], and the median PFS of the first-line and the second-line treatment population was 20.73 months (95% CI 9.82 to NR) and 4.27 months (95% CI 3.68 to NR), respectively. Most adverse events reported were of grade 1/2, and none were of grade 4/5. This is the first exploratory study of a fulvestrant and oral vinorelbine regimen in the treatment of HR+/HER2- recurrent and metastatic breast cancer. The combination chemo-endocrine therapy was efficacious, safe, and promising for patients with HR+/HER2- advanced breast cancer.

Oral vinorelbine and continuous low doses of cyclophosphamide in pediatric rhabdomyosarcoma: a real-world study.

Introduction: Metronomic maintenance therapy (MMT) has significantly improved the survival of patients with high-risk rhabdomyosarcoma in clinical trials. However, there remains a lack of relevant data on its effectiveness in real-world situations. Methods: We retrospectively retrieved data of 459 patients < 18years of age diagnosed with rhabdomyosarcoma at Sun Yat-sen University Cancer Center from January 2011 to July 2020 from our database. The MMT regimen was oral vinorelbine 25-40mg/m2 for twelve 4-week cycles on days 1, 8, and 15, and oral cyclophosphamide 25-50mg/m2 daily for 48 consecutive weeks. Results: A total of 57 patients who underwent MMT were included in the analysis. The median follow-up time was 27.8 (range: 2.9-117.5)months. From MMT to the end of follow-up, the 3-year PFS and OS rates were 40.6% ± 6.8% and 58.3% ± 7.2%, respectively. The 3-year PFS was 43.6% ± 11.3% in patients who were initially diagnosed as low- and intermediate-risk but relapsed after comprehensive treatment (20/57), compared with 27.8% ± 10.4% in high-risk patients (20/57) and 52.8% ± 13.3% in intermediate-risk patients who did not relapse (17/57). The corresponding 3-year OS for these three groups was 65.8% ± 11.4%, 50.1% ± 12.9%, and 55.6% ± 13.6%, respectively. Conclusion: We present a novel study of MMT with oral vinorelbine and continuous low doses of cyclophosphamide in real-world pediatric patients with RMS. Our findings showed that the MMT strategy significantly improved patient outcomes and may be an effective treatment for high-risk and relapsed patients.

207P A doublet metronomic chemotherapeutic regimen with oral vinorelbine and capecitabine (mNC) in patients with metastatic HER2-negative breast cancer: A prospective phase II study in China

The long-term efficacy of oral metronomic vinorelbine + capecitabine (mNC) in the treatment of Chinese patients with HER-2 negative metastatic breast cancer (MBC) stays unclear. Thus, we conducted a phase II trial to assess the efficacy and safety of mNC in patients with HER-2 negative MBC in China. The eligible patients with HER2-negative MBC received oral metronomic vinorelbine 40 mg on day 1, day 3, day 5 every week and capecitabine 500mg three times daily (tid) after meals every 3 weeks until disease progression or unacceptable toxicity occurred, or withdraw of consent. The primary endpoint was 1-year progression-free survival (PFS) rate. Objective response rate (ORR) (complete and partial response [CR + PR]) and disease control rate (DCR) (CR + PR + stable disease [SD]), clinical benefit rate (CBR) (CR + PR + SD ≥ 6 months) and toxicities comprised the secondary endpoints. Analyses were carried out on the intention-to-treat (ITT) population. The Kaplan-Meier plot was utilized to create median PFS plots. A log-rank test was utilized to compare PFS between the two groups. Univariable Cox proportional regression analysis was conducted to assess the association between various patients or tumor characteristics and disease progression. 29 patients with HER2-negative MBC were enrolled. 17 patients received mNC as first-line chemotherapy , 12 patients received mNC as second-line and 1 patient received mNC as > second-line. The median follow-up time was 25.4 months. The CBR, ORR and DCR were 62.1%, 31.0% and 96.6%, respectively. The mPFS was 12.5 months (range, 1.1-28.1). 1-year PFS rate was 54.1%. Subgroup analysis showed CBR was 64.6% and 58.3% in first-and second-line subgroups, respectively. The mPFS was 15.5 months for first-line and 11.2 months for second-line subgroup. 1-year PFS rate was 65.2% for first-line and 41.6% for second-line subgroup. The most common grade 3/4 AEs included neutropenia (10.3%) and nausea/vomiting (6.9%). A doublet metronomic chemotherapeutic regimen with oral mNC is a well-tolerated and effective anti-tumor regimen for HER2-negative MBC in China.

Oral vinorelbine in young patients with desmoid-type fibromatosis.

Desmoid-type fibromatosis are rare intermediate tumors in children and adolescents. Owing to local aggressiveness and relapse, systemic treatment for symptomatic advanced or progressive forms is recommended. Following promising results in adult patients, oral vinorelbine is investigated in young patients. A retrospective review of young patients (<25 years old) with advanced or progressive desmoid type fibromatosis treated with oral vinorelbine in eight large centers of the Société Française des Cancers de l'Enfant was performed. In addition to tumor assessment according to RECIST 1.1, pre-treatment and during-treatment imagery were reviewed centrally to assess tumor volume and estimate fibrosis score through the change in percentage in hypoT2 signal intensity. From 2005 to 2020, 24 patients (median age 13.9 years [range, 1.0-23.0]) received oral vinorelbine. Median number of prior systemic lines of treatment was 1 (range, 0-2), mainly based on intravenous low dose methotrexate and vinblastine. Before vinorelbine initiation, all patients had a progressive disease: radiological for 19, radiological and clinical (pain) for three and only clinical for two. Oral vinorelbine was delivered for a median duration of 12 months (range, 1-42). The toxicity profile was favorable, with no grade 3-4 event. Overall response estimated on 23 evaluable patients according to RECIST 1.1 criteria was three partial responses (13%), 18 stabilization (78%) and two progressive disease (9%). Overall progression-free survival was 89.3% (95% confidential intervals 75.2-100) at 24 months. Four stable tumors according to standard RECIST criteria displayed a partial response with > 65% tumor volume reduction. Among 21 informative patients, the estimated fibrosis score decreased for 15 patients, was stable for four patients and increased for two patients. Oral vinorelbine seems to be effective to control advanced or progressive desmoid type fibromatosis in young patients, with a well-tolerated profile. These results support testing this drug as first-line alone or in combination to improve response rate while preserving quality of life.

56P Pooled analysis of 4 studies evaluating weekly oral vinorelbine in patients with locally advanced or metastatic non-small cell lung cancer

56P Pooled analysis of 4 studies evaluating weekly oral vinorelbine in patients with locally advanced or metastatic non-small cell lung cancer

Abstract P3-02-07: Combined Chemo-endocrine Therapy Maybe a New Option for HR+/HER2− Advanced Breast Cancer: A Prospective, Single-center Clinical Study of Fulvestrant plus Oral Vinorelbine

Abstract Background Fulvestrant have demonstrated synergistic antitumor effect with chemotherapy regimen. This study evaluates the efficacy and safety of Fulvestrant with Vinorelbine in patients with hormone receptor positive (HR+)/human epidermal growth factor receptor-2-negative (HER2−) recurrent or metastatic breast cancer. Methods In this prospective, single-arm and investigator-initiated clinical study, patients with recurrent or metastatic HR+/HER2− breast cancer after the first line adjuvant endocrine therapy for &amp;gt; 1 year were eligible, in which the subjects of the first line was defined as the patients with recurrence and metastasis after adjuvant endocrine therapy for over 1 year and did not receive treatment for the recurrence and metastasis and the second-line defined as the patients who had disease progression after receiving first-line endocrine therapy or first-line chemotherapy). Patients were administered i.m. Fulvestrant 500mg (day 1 per cycle for 28 days) and oral Vinorelbine (60 mg/m2 on day 1, 8 and 15 of each cycle). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and safety. The Kaplan–Meier method and log-rank test were used to evaluate PFS and OS. Results Total 38 HR+/HER2- advanced breast cancer patients with median follow-up time (25.1 months) were enrolled in, and median PFS [9.86 months (95% CI: 7.2, 23.13)] were discovered. The median PFS of the first-line and the second-line treatment population were 20.73 months (95% CI: 9.82, NR) and 4.27 months (95% CI: 3.68, NR), respectively. The median OS of the intent-to-treat (ITT) and the first-line treatment population were not reached, and the OS of the second-line treatment was 28.2 months (95% CI: 11.5, NR). The ORR of the ITT population was 39.47% (95% CI: 23.93, 55.01). The ORR of the patients receiving first-line and second-line treatments were 44.44% (95% CI: 25.70, 63.19) and 27.27% (95% CI: 0.95, 53.59), respectively. The DCR of ITT population was 92.11% (95% CI: 83.54, 100.00)], and the median DoR was approximately 15.33 months (95% CI: 7.23, 22.54)]. In the safety analysis, most of the adverse events were grade of 1/2, and none of grade 4/5 adverse events were reported. Conclusion This is the first exploratory study of Fulvestrant with oral Vinorelbine regimen in the treatment of HR+/HER2− recurrent and metastatic breast cancer conducted worldwide. The combinative chemo-endocrine therapy was efficacious, safe and promising for patients with HR+/HER2− advanced breast cancer. Citation Format: Xue Wang, Jian Yue, Jiayu Wang, Pin Zhang, Fei Ma, Binghe Xu, Peng Yuan. Combined Chemo-endocrine Therapy Maybe a New Option for HR+/HER2− Advanced Breast Cancer: A Prospective, Single-center Clinical Study of Fulvestrant plus Oral Vinorelbine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-07.

Safety and efficacy of second-line metronomic oral vinorelbine-atezolizumab combination in stage IV non-small-cell lung cancer: An open-label phase II trial (VinMetAtezo)

ObjectiveTo evaluate the safety and efficacy of second-line metronomic oral vinorelbine–atezolizumab combination for stage IV non-small-cell lung cancer. MethodsThis was a multicenter, open-label, single-arm Phase II study performed in patients with advanced NSCLC without activating EGFR mutation or ALK rearrangement who progressed after first-line platinum-doublet chemotherapy. Combination treatment was atezolizumab (1200 mg IV day 1, every 3 weeks) and oral vinorelbine (40 mg, 3 times by week). The primary outcome was progression-free survival (PFS) during the 4-month follow-up from the first dose of treatment. Statistical analysis was based on the exact single-stage Phase II design defined by A’Hern. Based on literature data, the Phase III trial threshold was set at 36 successes in 71 patients. Results71 patients were analyzed (median age, 64 years; male, 66.2%; ex-smokers/active smokers, 85.9%; ECOG performance status 0–1, 90.2%; non-squamous NSCLC, 83.1%; PD-L1 ≥ 50%, 4.4%). After a median follow-up of 8.1 months from treatment initiation, 4-month PFS rate was 32% (95% CI, 22–44), i.e. 23 successes out 71 patients. OS rate was 73.2% at 4 months and 24.3% at 24 months. Median PFS and OS were 2.2 (95% CI, 1.5–3.0) months and 7.9 (95% CI, 4.8–11.4) months, respectively. Overall response rate and disease control rate at 4 months were 11% (95% CI, 5–21) and 32% (95% CI, 22–44), respectively. No safety signal was evidenced. ConclusionMetronomic oral vinorelbine-atezolizumab in the second-line setting did not achieve the predefined PFS threshold. No new safety signal was reported for vinorelbine-atezolizumab combination.

CHEOPS trial: a GINECO group randomized phase II assessing addition of a non-steroidal aromatase inhibitor to oral vinorelbine in pre-treated metastatic breast cancer patients

BackgroundThe objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy, oral vinorelbine, 50 mg, three times a week for pre-treated, HR + /HER2- metastatic breast cancer patients.MethodsIn this multicentric phase II study, patients had to have progressed on AI and one or two lines of chemotherapy. They were randomized between oral vinorelbine (Arm A) and oral vinorelbine with non-steroidal AI (Arm B).Results121 patients were included, 61 patients in Arm A and 60 patients in Arm B. The median age was 68 years. 109 patients had visceral metastases. They all had previously received an AI. The study had been prematurely stopped following the third death due to febrile neutropenia. Median PFS trend was found to be different with 2.3 months and 3.7 months in Arm A and Arm B, respectively (HR 0.73, 95%CI 0.50–1.06, p value = 0.0929). No statistical difference was shown in OS and better tumor response. 56 serious adverse events corresponding to 25 patients (21%) were reported (respectively, 12 (20%) versus 13 (22%) for arms A and B) (NS).ConclusionThe addition of AI to oral vinorelbine over oral vinorelbine alone in aromatase inhibitor-resistant metastatic breast cancer was associated with a non-significant improvement of PFS. Several unexpected serious adverse events were reported. Metronomic oral vinorelbine schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 &lt; 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56-92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3-4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 &lt; 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (&gt;70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.

478P Metronomic oral vinorelbine (MOV) combined with tremelimumab (T) + durvalumab (D): Results of the tumor mutational burden-high (TMB-h) and/or microsatellite instability-high (MSI-h) cohort of the MOVIE study

Both TMB-h and MSI-h result in a high rate of neoantigens, which may favor the efficacy of immune checkpoint inhibitors. Pembrolizumab (an anti- PD1) has been FDA-approved in MSI-h/TMB-h advanced solid tumor (AST) with an agnostic indication. MOVIE is a multi-cohort phase I/II study examining the combination of T+D+MOV in AST. We report here the results of the TMB-h and/or MSI-h cohort in miscellaneous AST. Patients (pts) were eligible with TMB-h (as determined by a local molecular tumor board), and/or MSI-h (by locally performed PCR and IHC test). T was administered for up to 4 cycles (cy) and D for up to 26 cy (or 24 months (mo) whichever is longer). MOV was administered at 40 mg orally thrice weekly, until disease progression (PD). Primary endpoint of phase II part was clinical benefit rate (CBR= CR, PR or SD > 24 wks) according to RECIST 1.1. Continuous monitoring of efficacy was planned using a Bayesian approach, with a futility bound of 40%. Secondary objectives included safety, ORR, DOR, PFS and OS. 30 pts were included in the cohort: 10 MSI-h, 13 TMB-h and 7 both. Median age was 65 (35; 83). Median number of previous metastatic lines of systemic treatment was 1.5 (0 ; 10). As of April 2022, 9 pts were on treatment, 17 stopped for PD and 4 for unacceptable toxicity; median follow-up was 9.1 mo (1.4 – 24.1). Clinical benefit was observed for 15 pts: 1 CR, 9 PR, and 5 SD > 24 wks. Bayesian estimations of the mean CBR (95%(CI)) according to the prior distributions defined are reported in the table. 21 (70%) pts had grade ≥2 treatment-related adverse events, including 9 pts (30%) with grade ≥3. No toxic death was recorded. Bayesian estimations of the mean CBR.Table: 478PPrior non-informative beta (1,1)Informative Prior Beta (5.7,5.7)Less informative optimism Beta (1.3,1.3)Mean [95% CI]50% [33.1% ; 66.9%]50% [35.0% ; 65.0%]50% [33.2% ; 66.8%] Open table in a new tab T+D+MOV has promising activity in TMB-h and or MSI-h cohort. Toxicity profile was consistent with previous reports of T+D combination or MOV.

216MO A randomized phase II trial of metronomic oral vinorelbine plus cyclophosphamide and capecitabine (VEX) vs weekly paclitaxel (P) as first- or second-line treatment in patients (pts) with ER+/HER2- metastatic breast cancer (MBC): The METEORA-II trial (IBCSG 54-16)

METEORA-II was designed to test the concept of the metronomic VEX regimen administered for as long as the pt has the possibility of deriving a benefit from it, in comparison with weekly P, for pts with ER+/HER2- MBC candidates for chemotherapy (CT). Time to treatment failure (TTF) was chosen as primary endpoint, as CT may be stopped due to lack of tolerability, lack of efficacy or pt preference.