Randomized phase II trial of olaparib + pembrolizumab versus olaparib alone as maintenance therapy in metastatic pancreatic cancer patients with germline BRCA1 or BRCA2 (gBRCA1/2+) mutations: SWOG S2001.

TPS447 Background: Olaparib was approved in 2019 as maintenance therapy for g BRCA1/2+ metastatic pancreatic cancer (mPDA) patients (pts). The POLO trial showed an improvement in median progression free survival (mPFS) with olaparib compared to placebo (7.4 versus 3.8 months) for g BRCA1/2+ mPDA pts following either stable disease/response on first-line platinum chemotherapy. Preclinical studies have demonstrated that PARP inhibitors modulate the immune microenvironment by increasing genomic instability, PD-L1 expression and activating the immune inflammatory stimulator of interferon genes (STING) pathway. Several clinical studies in solid tumors have shown preliminary efficacy with the combination of PARP plus immune checkpoint inhibitors. Based upon these data, SWOG S2001 aims to further improve the PFS of g BRCA1/2+ mPDA pts. Methods: S2001 was developed in collaboration with the Alliance and was activated in SWOG in October 2020. mPDA pts with gBRCA1/2 mutations identified with standard of care germline genetic testing will be eligibleif no progression after receiving 4 to 6 months of platinum chemotherapy (FOLFIRINOX, FOLFOX or gemcitabine/cisplatin). Zubrod performance status (PS) 0 or 1 pts are eligible. Pts will be stratified according to first line chemotherapy, PS 0 versus 1, and disease status after first-line treatment. The primary objective of this study is to evaluate the PFS of mPDA pts treated with olaparib + pembrolizumab compared to olaparib alone as maintenance therapy. Based upon the POLO trial, we expect a mPFS of 7 months in the control arm. Targeting a mPFS of 11.7 months in the experimental arm (hazard ratio 0.6) and assuming 15 months follow-up, 80% power and a 1-sided alpha=0.10, this design requires 78 evaluable pts to be accrued over 3 years. Prospective serial blood samples will be collected to bank DNA and RNA for future correlative studies. Support:NIH/NCI grants U10CA180888 and U10CA180819. Clinical trial information: TBD.

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Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819878660 ◽

2019 ◽

Vol 12 ◽

pp. 175628481987866 ◽

Cited By ~ 3

Author(s):

Nicolas Williet ◽

Angélique Saint ◽

Anne-Laure Pointet ◽

David Tougeron ◽

Simon Pernot ◽

...

Keyword(s):

Pancreatic Cancer ◽

Propensity Score ◽

Liver Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

First Line ◽

First Line Therapy ◽

Reverse Sequence ◽

Metastatic Sites

Background: Folfirinox (FFX) and gemcitabine/nab-paclitaxel (GN) are both standard first-line treatments in patients with metastatic pancreatic cancer (mPC). However, data comparing these two chemotherapeutic regimens and their sequential use remain scarce. Methods: Data from two independent cohorts enrolling patients treated with FFX ( n = 107) or GN ( n = 109) were retrospectively pooled. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was the secondary endpoint. A propensity score based on age, gender, performance status (PS), and presence of liver metastases was used to make groups comparable. Results: In the whole study population, OS was significantly higher in FFX (14 months; 95% CI: 10–21) than in GN groups (9 months; 95% CI: 8–12) before ( p = 0.008) and after ( p = 0.021) adjusting for age, number of metastatic sites, liver metastases, peritoneal carcinomatosis and CA19.9 level at baseline. PFS tends to be higher in FFX (6 months) than GN groups (5 months; p = 0.053). After matching ( n = 49/group), patients were comparable for all baseline characteristics including PS. In the matched population, there was a trend toward greater OS in patients treated with FFX (HR = 0.67; p = 0.097). However, survival in each group was not solely a result of the first-line regimen. The proportion of patients who were fit for GN after FFX failure (FFX–GN sequence) was higher (46.9%) than the reverse sequence (20.4%; p = 0.01), which suggests a higher feasibility for the FFX–GN sequence. Corresponding median OS were 19 months versus 9.5 months, respectively ( p = 0.094). Conclusion: This study shows greater OS with FFX than with GN in patients with mPC. GN after FFX failure appears more feasible than the reverse sequence.

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Systemic Therapy for Metastatic Pancreatic Cancer

Current Treatment Options in Oncology ◽

10.1007/s11864-021-00895-4 ◽

2021 ◽

Vol 22 (11) ◽

Author(s):

Thomas J. Ettrich ◽

Thomas Seufferlein

Keyword(s):

Pancreatic Cancer ◽

Checkpoint Inhibitors ◽

Parp Inhibitor ◽

Performance Status ◽

Single Agent ◽

Metastatic Pancreatic Cancer ◽

Line Treatment ◽

First Line ◽

Platinum Based Chemotherapy ◽

First Line Treatment

Opinion statementPancreatic cancer is mainly diagnosed at an advanced, often metastatic stage and still has a poor prognosis. Over the last decades, chemotherapy of metastatic pancreatic cancer (mPDAC) has proven to be superior to a mere supportive treatment with respect to both survival and quality of life. Recently, even sequential treatment of mPDAC could be established. Options for first-line treatment are combination chemotherapy regimens such as FOLFIRINOX and gemcitabine plus nab-paclitaxel when the performance status of the patient is good. For patients with poorer performance status, gemcitabine single-agent treatment is a valid option. Recently, the PARP inhibitor olaparib has been demonstrated to improve progression-free survival when used as a maintenance treatment in the subgroup of patients with mPDAC and a BRCA1/-2 germ line mutation having received at least 16 weeks of platinum-based chemotherapy. This group of patients also benefits from platinum-based chemotherapy combinations. Therefore, the BRCA1/-2 stats should be examined early in patients with mPDAC even when the occurrence of these mutations is only about 5% in the general Caucasian population. After the failure of first-line treatment, patients should be offered a second-line treatment if their ECOG permits further treatment. Here, the combination of 5-FU/FA plus nanoliposomal irinotecan has shown to be superior to 5-FU/FA alone with respect to overall survival. Immune checkpoint inhibitors like PD1/PD-L1 mAbs are particularly efficacious in tumors with high microsatellite instability (MSI-h). Limited data in mPDACs shows that only a part of the already small subgroup of MSI-H mPDACs (frequency about 1%) appears to benefit substantially from a checkpoint inhibitor treatment. The identification of further subgroups, e.g., tumors with DNA damage repair deficiency, gene fusions, as well as novel approaches such as tumor-organoid-informed treatment decisions, may further improve therapeutic efficacy.

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Anlotinib Plus Toripalimab and Nab-Paclitaxel in Patients with Locally Advanced or Metastatic Pancreatic Cancer: Study Protocol for An Open-Label, Non-Randomized, Phase II Study (ATNPA)

10.21203/rs.3.rs-1076724/v1 ◽

2021 ◽

Author(s):

Jingwen Chen ◽

Yiqian Liu ◽

Yizhi Zhu ◽

Shiyun Cui ◽

Chongqi Sun ◽

...

Keyword(s):

Pancreatic Cancer ◽

Maintenance Therapy ◽

Kinase Inhibitor ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Second Line ◽

First Line ◽

Open Label ◽

Combination Strategy

Abstract Background There have not been standard second-line or maintenance regimens with definite survival benefits so far for patients with pancreatic carcinoma who have lost the opportunity of curable resections or failed first-line chemotherapy. Anlotinib, a potent small-molecule tyrosine kinase inhibitor, exhibits anti-angiogenic and anti-tumour effects by specifically binding to multiple targets such as VEGFR, FGFR, PDGFR, c-Kit and Ret. Toripalimab, a novel anti-PD-1 mAb, has been proved to significantly prolong progression-free survival (PFS) and overall survival (OS) in various solid tumours with manageable toxicities when combining with cytotoxic chemotherapy. We design this study to assess the combination of anlotinib, toripalimab and nab-paclitaxel as a second-line or maintenance therapy for locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (MPC). Patients and Methods: This is an open-label, non-randomized, single-arm phase Ⅱ study, aimed at evaluating the efficacy and safety profile of the above-mentioned combination strategy in first-line therapy-failed LAPC or MPC. Totally 53 patients are to be enrolled and receive anlotinib (12 mg, po. qd.) plus toripalimab (240 mg, ivgtt. q3w.) and nab-paclitaxel (125 mg/m2, ivgtt, d1, d8) every 3 weeks as a cycle until disease progression or intolerable adverse events. The primary endpoint is PFS. Secondary end points include OS, disease control rate (DCR), object response rate (ORR), quality of life (QoL) and safety. Enrollment started in April 2021, and follow-up will be finished in April 2023. Discussion and Significance: Combination of anlotinib, toripalimab and nab-paclitaxel may promote vessel normalization and drug delivery, and activate the immune response, thus exerting synergistic anti-tumour effects and counteracting the immunosuppressive microenvironment of pancreatic cancer. As the first intending to assess this combination in pancreatic cancer, this study will provide comprehensive evidence for second-line or maintenance therapy of LAPC and MPC. Trial registration: ClinicalTrials.gov: ATNPA, NCT04718701. Registered January 22, 2021. (https://clinicaltrials.gov/ct2/show/NCT04718701?term=NCT04718701&draw=2&rank=1)

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Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study

Cancers ◽

10.3390/cancers11070939 ◽

2019 ◽

Vol 11 (7) ◽

pp. 939 ◽

Cited By ~ 1

Author(s):

Caterina Vivaldi ◽

Lorenzo Fornaro ◽

Carla Cappelli ◽

Irene Pecora ◽

Silvia Catanese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Tumor Shrinkage ◽

First Line ◽

Free Survival ◽

Depth Of Response ◽

Early Tumor Shrinkage ◽

Early Tumor

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

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Efficacy of chemotherapy in patients with recurrent pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.466 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 466-466 ◽

Cited By ~ 1

Author(s):

Akihiro Ohba ◽

Hideki Ueno ◽

Yuji Inagaki ◽

Yasunari Sakamoto ◽

Shunsuke Kondo ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Chemotherapy ◽

Liver Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Similar Efficacy ◽

Lower Percentage ◽

First Line ◽

Recurrent Pancreatic Cancer ◽

Line Chemotherapy

466 Background: Gemcitabine (GEM) plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) are standard first-line chemotherapy regimens for metastatic pancreatic cancer (MPC) patients. GEM and S-1 are also used for these patients in Japan. However, the phase 3 trials included a small proportion of recurrent pancreatic cancer (RPC) patients, and patients who had received adjuvant chemotherapy were excluded. In clinical practice, RPC is treated in the same way as MPC. The aim of this study is to compare the efficacy of chemotherapy between RPC and MPC. Methods: We retrospectively analyzed the patients with RPC or MPC who received GnP, FFX, GEM, or S-1 as first-line chemotherapy between January 2014 and March 2016 in our institution. RPC was defined as pancreatic cancer with recurrence after R0 or R1 resection. Overall survival (OS), progression-free survival (PFS), response rate (RR), and disease control rate (DCR) were evaluated. Multivariate analyses of OS were performed with the use of a Cox proportional-hazard model. Results: A total of 181 patients, 40 RPC and 141 MPC, were selected in this study. RPC and MPC groups were similar with respect to age, sex, and performance status (PS). However, the RPC group had lower percentage of liver metastases (P < 0.001). The regimens were GnP/FFX/GEM/S-1: 10/3/20/7 in the RPC group and 37/34/67/3 in the MPC group, respectively. In the RPC group, 31 of 40 patients had received adjuvant chemotherapy; S-1/GEM: 24/7. The median OS was 16.6 months in the RPC group as compared with 9.7 months in the MPC group (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.37–1.10, P = 0.11). The median PFS was 4.8 months in the RPC group and 4.4 months in the MPC group (HR 0.86, 95% CI 0.57–1.30, P = 0.47). The RR was 10% versus 14% (P = 0.79), the DCR was 50% versus 52% (P = 0.86), in the two groups, respectively. Multivariate analysis showed PS (HR 2.19, 95% CI 1.38–3.49) and liver metastases (HR 2.34, 95% CI 1.47–2.34) were independent predictors of OS. On the other hand, RPC or MPC was not found to be an independent prognostic factor (HR 1.19, 95% CI 0.67–2.13). Conclusions: It is suggested that chemotherapy in RPC may have similar efficacy compared to MPC. The relatively longer OS in the RPC group seems to associate with the lower percentage of liver metastases.

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Activity and safety of Nab-FOLFIRI and Nab-FOLFOX as first-line treatment for metastatic pancreatic cancer (phase II NabucCO study).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.351 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 351-351 ◽

Cited By ~ 1

Author(s):

Elisa Giommoni ◽

Evaristo Maiello ◽

Vanja Vaccaro ◽

Ermanno Rondini ◽

Caterina Vivaldi ◽

...

Keyword(s):

Pancreatic Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Maximum Tolerated Dose ◽

Dose Finding ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

First Line ◽

Open Label ◽

Grade 3

351 Background: FOLFIRINOX is an approved regimen for metastatic pancreatic cancer (mPC). We performed a modification in FOLFIRINOX schedule, using nab-paclitaxel (nab-p) to obtain two regimens that could be as effective and less toxic than the original triplet. NabucCO study was a randomized phase II trial to assess activity and toxicity of nab-p instead of either oxaliplatin (Nab-FOLFIRI) or irinotecan (Nab-FOLFOX) in first line setting. Previous dose–finding NabucCO study defined that maximum tolerated dose of nab-p with FOLFIRI is 120 mg/m2, and with FOLFOX is 160 mg/m2. Methods: The study was a 1:1 parallel arm, open label, not comparative one to assess overall response rate (ORR) of Nab-FOLFIRI and Nab-FOLFOX as primary end-point. Patients (pts) with PS 0-1, untreated for mPC were randomized to receive leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2, irinotecan 180 mg/m2 plus nab-p 120 mg/m2 (arm A) or leucovorin 400 mg/m2, 5FU bolus 400 mg/m2, 5FU 48h ci 2400 mg/m2 and oxaliplatin 85 mg/m2 iv plus nab-p 160 mg/m2 (arm B) every 2 weeks for up to 12 cycles. Secondary end points were clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS), and safety. Results: From November 2015 to January 2017, 84 pts were treated (42 for each arm). Median age was 60 years (29-65) in arm A and 64 years (47-64) in arm B. The ORR was 31 % for both schedules, with a CBR of 69% and 71%, respectively. At a median follow-up of 11.4 months for arm A and 14.5 months for arm B (censored on august, 31th 2017), 1-year survival is 41% and 50%, respectively. For Nab-FOLFIRI PFS and mOS were 6 months (90% CI: 4.9-8.0) and 13.2 months (90% CI: 8.3-14.8), while in Nab-FOLFOX were 5.6 months (90% CI:4.9-7.2) and 10.8 months (90% CI: 8.4-12.8). Grade ≥3 toxicities in arm A were neutropenia (19%) and febrile neutropenia (12%). In arm B, main grade ≥3 toxicities were neutropenia (29%), fatigue (14%), peripheral neuropathy (7%). No toxic death were registered. Conclusions: Nab-FOLFIRI and Nab–FOLFOX demonstrated a similar activity to FOLFIRINOX, with better safety profile in terms of neutropenia, fatigue and neuropathy. These results could justify a future phase III evaluation. Clinical trial information: NCT02109341.

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PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4665 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4665-TPS4665

Author(s):

Jiujie Cui ◽

Jiayu Yao ◽

Yu Wang ◽

Yiyi Liang ◽

Yongchao Wang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Checkpoint Inhibitors ◽

Tumor Therapy ◽

Advanced Pancreatic Cancer ◽

Metastatic Pancreatic Cancer ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

First Line Treatment

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .

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Patterns of care in metastatic pancreatic cancer: patient selection in clinical routine

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284819877635 ◽

2019 ◽

Vol 12 ◽

pp. 175628481987763 ◽

Cited By ~ 2

Author(s):

Werner Scheithauer ◽

Paul Martin Putora ◽

Birgit Grünberger ◽

Wolfgang Eisterer ◽

Ewald Wöll ◽

...

Keyword(s):

Pancreatic Cancer ◽

Decision Trees ◽

Patient Selection ◽

Performance Status ◽

Treatment Options ◽

Metastatic Pancreatic Cancer ◽

Decision Criteria ◽

First Line ◽

Clinical Routine ◽

Treatment Algorithms

Background: The management of patients with metastatic pancreatic cancer (mPC) is challenging, and the optimal treatment strategy is debated among experts. In an attempt to identify treatment decision criteria and to investigate variations in the first-line management of this disease, we performed an analysis of treatment algorithms among experts in the field of pancreatic cancer. The aim of this study was to identify relevant criteria in the complex process of patient selection and decision making for the management of mPC patients. Methods: Experts from the ABCSG (Austrian Breast and Colorectal Cancer Study Group) Pancreatic Cancer Club were contacted and agreed to participate in this analysis. Eight experts from seven centers in Austria provided their decision algorithms for the first-line treatment of patients with mPC. Their responses were converted into decision trees based on the objective consensus methodology. The decision trees were used to identify consensus and discrepancies. Results: The final treatment algorithms included four decision criteria (performance status, age, comorbidities, and symptomatic disease) and six treatment options: mFOLFIRINOX, gemcitabine + nab-paclitaxel, gemcitabine mono, 5-FU mono, gemcitabine/erlotinib, and best supportive care (BSC). Conclusions: We identified consensus for the treatment of young and fit patients with mFOLFIRINOX. With higher age and reduced performance status, gemcitabine + nab-paclitaxel was increasingly used. For patients with Eastern Co-operative Oncology Group Performance Status (ECOG PS) 4, BSC was the treatment of choice. Among experts, different decision criteria and treatment options are implemented in clinical routine. Despite multiple options in current recommendations, a consensus for specific recommendations was identified.

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Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

Scientific Reports ◽

10.1038/s41598-020-76465-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Giandomenico Roviello ◽

Monica Ramello ◽

Martina Catalano ◽

Alberto D’Angelo ◽

Raffaele Conca ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Response Rate ◽

Progression Free Survival ◽

Metastatic Pancreatic Cancer ◽

Common Side Effect ◽

First Line ◽

Free Survival ◽

Grade 3 ◽

Toxicity Criteria

Abstract Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

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Safety and efficacy of capecitabine (C) plus bevacizumab (B) as first-line in metastatic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1013 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1013-1013 ◽

Cited By ~ 26

Author(s):

G. Sledge ◽

K. Miller ◽

C. Moisa ◽

W. Gradishar

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Performance Status ◽

Metastatic Breast ◽

Progression Free Survival ◽

Primary Objective ◽

First Line ◽

Ecog Performance Status ◽

Eligibility Criteria ◽

Grade 3

1013 Background: C alone has good activity and tolerability in metastatic breast cancer (MBC) and when combined with docetaxel improves response and survival. C combined with B in heavily pretreated MBC improved the response rate but not PFS. In untreated MBC, the addition of B to chemotherapy significantly improves progression-free survival (PFS) which suggests that B, is most effective in early disease. Methods: Primary objective of this single-arm, 2-phase study, is to evaluate PFS in MBC patients receiving first-line treatment with C 1,000 mg/m2 twice daily on days 1–15 (28 doses) and B 15 mg/kg on day 1. Treatment was repeated every 21 days until progression. Eligibility criteria included HER2-negative MBC previously untreated for metastatic disease; ECOG performance status =1; no prior anti-angiogenic or oral fluoropyrimidine therapy. A sample size of 109 patients (including dropouts) was required to give 90% power to test an improvement from 4 months median PFS to 5.6 months with the two-sided test (a 5%) Results: At data cut-off, 103 patients had received study medication. Present results are based on 103 patients (ITT population), except tumor response which is based on 91 patients who had response evaluation. The average # of cycles received in first phase is 6.8. 84 pts.are alive at this time. 38.5% (35/91) pts. have had a response: complete response 5.5%; partial response 33.0%. Stable disease is 42.9% with 81.4% clinical benefit. Planned dose received is 77.7 % for C and 99.0 % for B. The majority of adverse events (AEs) were mild or moderate. The most common grade 3 AEs were hand-foot syndrome (13%) and pain (10%); grade 4 pulmonary embolism occurred in 2% in the first phase of the study. Conclusions: Updated results with longer follow-up including toxicity, TTP and PFS will be presented at the meeting. It appears that in first-line C+B is active for MBC and is well tolerated, with few grade 3/4 toxicities. [Table: see text]

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