Second-line Chemotherapy In Patients Research Articles

Efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma

The efficacy of second-line chemotherapy in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC) is unclear. This study aimed to evaluate the efficacy of second-line chemotherapy in patients with pulmonary LCNEC. We retrospectively reviewed patients with pulmonary LCNEC or possible LCNEC (pLCNEC) who received platinum-based chemotherapy as the first-line treatment. Among these patients, we evaluated the efficacy of second-line treatment by comparing patients with small cell lung cancer (SCLC group). Of the 61 patients with LCNEC or pLCNEC (LCNEC group) who received first-line chemotherapy, 39 patients were treated with second-line chemotherapy. Among the 39 patients, 61.5% received amrubicin monotherapy. The median progression-free survival (PFS) and overall survival (OS) in the LCNEC groups were 3.3 and 8.3 months, respectively. No significant differences in the PFS (hazard ratio [HR]: 0.924, 95% confidence interval [CI] 0.647–1.320; P = 0.664) and OS (HR: 0.926; 95% CI 0.648–1.321; P = 0.670) were observed between the LCNEC and SCLC groups. In patients treated with amrubicin, the PFS (P = 0.964) and OS (P = 0.544) were not different between both the groups. Second-line chemotherapy, including amrubicin, may be considered as a treatment option for patients with pulmonary LCNEC.

Real-world Study on the Effect of PARPi as Maintenance Therapy on Platinum Sensitivity after First- and Second-line Chemotherapy in Patients with Recurrent High-grade Serous Epithelial Ovarian Cancer.

This study investigated the effect of poly(ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy after first- and second-line chemotherapy on platinum sensitivity in patients with recurrent high-grade serous epithelial ovarian cancer (rHGSOC). This study retrospectively analyzed 172 patients with rHGSOC treated at Zhejiang Cancer Hospital and Jiaxing Maternity and Child Health Care Hospital between January 2017 and December 2021. The 1st-PARPi group comprised patients who received a PARPi as maintenance therapy after first-line chemotherapy (n=23), and the 1st-control group comprised those who did not (n = 105). Similarly, the 2nd-PARPi group comprised patients not given a PARPi in their first-line treatment (n = 30), and the 2nd-control group comprised those who were given a PARPi (n = 89). Among the 23 patients in the 1st-PARPi group and the 105 patients in the 1st-control group, nine and 99 were platinum-sensitive, and 14 and six were platinum-resistant, respectively (hazard ratio [HR]: 14.46, P < 0.0001). Among the 30 patients in the 2nd-PARPi group and 89 patients in the 2nd-control group, 10 and 71 were platinum-sensitive, and 20 and 18 were platinumresistant, respectively (HR: 4.37, P < 0.0001). Age, stage, residual tumor, the courses of platinumbased chemotherapy, and breast cancer susceptibility gene mutations were not associated with platinum sensitivity when using a PARPi as maintenance therapy after first- and second-line chemotherapy. Patients with rHGSOC using a PARPi were more likely to be platinum-sensitive and develop platinum resistance independent of PARPi duration. Care should be taken when using a PARPi as maintenance therapy after first- and second-line chemotherapy.

Importance of Progression-free Survival in Second-line Chemotherapy in Patients With Advanced or Recurrent Gastric Cancer.

Impact of second-line chemotherapy in unresectable advanced/recurrent gastric/esophagogastric junction cancer (AGC) remains unclear. This retrospective analysis aimed to identify factors affecting prognosis in chemotherapy for patients with AGC, including the importance of progression-free survival in second-line chemotherapy (PFS-2). Data from a total of 109 patients with AGC that received second-line treatment were analyzed with the aim of clarifying prognostic factors. Furthermore, the correlation between PFS-2 and clinical characteristics and the association between PFS-2 and inflammation-based and/or nutritional markers were investigated. Multivariate analysis identified the following prognostic factors: ECOG PS ≥1, presence of peritoneal dissemination, metastasis in two or more organs, and taxane use on second-line chemotherapy. Short PFS-2 was strongly associated with prognosis in the univariate analysis [hazard ratio (HR)=3.107, 95% confidence interval (CI)=1.969-4.904, p<0.001]. The duration of PFS-2 was significantly correlated with ECOG PS (p=0.019), liver metastasis rates (p=0.035) and taxane use on second-line chemotherapy (p=0.001). In addition, weight loss rate during first-line treatment (p=0.042), white blood cell count (p=0.008), C-reactive protein (p=0.032), c-reactive protein to albumin ratio (p=0.039), prognostic index (p=0.028), and modified Glasgow prognostic score (p=0.027) were significantly associated with the duration of PFS-2. The duration of PFS-2 significantly correlated with ECOG PS, liver metastasis, and taxane use on second-line treatment, and strongly affected OS. It was suggested that the presence of malnutrition and inflammation at the start of second-line therapy had a negative impact on PFS-2 and OS.

Safety and efficacy of amrubicin with primary prophylactic pegfilgrastim as second-line chemotherapy in patients with small cell lung cancer.

Amrubicin (AMR) regimens have shown efficacy as second-line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P-PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P-PEG as second-line chemotherapy for SCLC. We retrospectively reviewed patients with SCLC who received AMR as second-line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P-PEG in their regimen, patients (n = 60) were divided into P-PEG (n = 21) and non-P-PEG groups, and their clinical outcomes were evaluated. Median of AMR treatment cycles was five (range: 1-39 cycles) in P-PEG group and four (range: 1-15 cycles) in non-P-PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P-PEG group than in the non-P-PEG group. The objective response rates were 52.4% and 30.8%, and median progression-free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P-PEG and non-P-PEG groups, respectively. AMR with P-PEG as second-line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P-PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.

PROCARBAZINE, LOMUSTINE, VINCRISTINE FOR THE SECOND LINE TREATMENT OF GLIOBLASTOMA MULTIFORME

Abstract AIMS Most patients with glioblastoma recur despite surgery and post-operative chemoradiation. The optimal second line chemotherapy regime is not known. The aim of this study was to evaluate PCV chemotherapy given as second line treatment for glioblastoma. METHOD Data was collected for all patients with glioblastoma treated with second line PCV between 2009 and 2021 at the Norfolk and Norwich University Hospital. All underwent surgical resection either complete or incomplete resection followed by adjuvant radiotherapy and chemotherapy according to the Stupp or Perry A protocol. All received palliative PCV chemotherapy at recurrence. The Response Assessment in Neuro-Oncology (RANO) criteria were used to assess response to palliative PCV chemotherapy. Patient and disease related characteristics were described. Disease free survival from recurrence to death and survival outcomes were estimated using Kaplan-Meir method. RESULTS 70 patients were evaluated. Overall survival from surgery to death was 290 days (95%CI 245 to 318) Survival from disease progression to death was 182 days (95%CI 131 to 218). Subgroup analysis was performed for patients &amp;lt;65years and &amp;gt;65years. For patients &amp;lt;65 years N=51, median overall survival was 199 days (95%CI 142 to 353) p value 0.1246. For those &amp;gt;65 years N=16, median overall survival was 130.5 days (95%CI 93 to 227) CONCLUSIONS Using PCV as a second line chemotherapy for patients with glioblastoma is a reasonable approach. It is well tolerated and provides benefit for patients &amp;lt;65 years as well as older patients.

Avelumab vs Standard Second-Line Chemotherapy in Patients With Metastatic Colorectal Cancer and Microsatellite Instability

Only 1 randomized clinical trial has shown the superiority of immune checkpoint inhibitors in patients with deficient mismatch repair and/or microsatellite instability (dMMR/MSI) metastatic colorectal cancer (mCRC) in the first-line setting. To determine whether avelumab (an anti-programmed cell death ligand 1 antibody) improves progression-free survival (PFS) compared with standard second-line chemotherapy in patients with dMMR/MSI mCRC. The SAMCO-PRODIGE 54 trial is a national open-label phase 2 randomized clinical trial that was conducted from April 24, 2018, to April 29, 2021, at 49 French sites. Patients with dMMR/MSI mCRC who experienced progression while receiving standard first-line therapy were included in the analysis. Patients were randomized to receive standard second-line therapy or avelumab every 2 weeks until progression, unacceptable toxic effects, or patient refusal. The primary end point was PFS according to RECIST (Response Evaluation Criteria in Solid Tumours), version 1.1, evaluated by investigators in patients with mCRC and confirmed dMMR and MSI status who received at least 1 dose of treatment (modified intention-to-treat [mITT] population). A total of 122 patients were enrolled in the mITT population. Median age was 66 (IQR, 56-76) years, 65 patients (53.3%) were women, 100 (82.0%) had a right-sided tumor, and 52 (42.6%) had BRAF V600E-mutated tumors. There was no difference in patients and tumor characteristics between treatment groups. No new safety concerns in either group were detected, with fewer treatment-related adverse events of at least grade 3 in the avelumab group than in the chemotherapy group (20 [31.7%] vs 34 [53.1%]; P = .02). After a median follow-up of 33.3 (95% CI, 28.3-34.8) months, avelumab was superior to chemotherapy with or without targeted agents with respect to PFS (15 [24.6%] vs 5 [8.2%] among patients without progression; P = .03). Rates of PFS rates at 12 months were 31.2% (95% CI, 20.1%-42.9%) and 19.4% (95% CI, 10.6%-30.2%) in the avelumab and control groups, respectively, and 27.4% (95% CI, 16.8%-39.0%) and 9.1% (95% CI, 3.2%-18.8%) at 18 months. Objective response rates were similar in both groups (18 [29.5%] vs 16 [26.2%]; P = .45). Among patients with disease control, 18 (75.7%) in the avelumab group compared with 9 (19.1%) in the control group had ongoing disease control at 18 months. The SAMCO-PRODIGE 54 phase 2 randomized clinical trial showed, in patients with dMMR/MSI mCRC, better PFS and disease control duration with avelumab over standard second-line treatment, with a favorable safety profile. ClinicalTrials.gov Identifier: NCT03186326.

233P Treatment pattern and outcomes for the first two lines of chemotherapy in patients diagnosed with metastatic triple-negative breast cancer, results from the Dutch SONABRE Registry

We assessed the use and outcomes of first- and second-line chemotherapy in patients diagnosed with metastatic triple-negative breast cancer (mTNBC). All consecutively diagnosed patients with mTNBC in 2014-2020 in ten Dutch hospitals were retrieved from the SONABRE registry (NCT-03577197). Last follow-up was collected in 2022. The proportion of patients starting a specific line of therapy was assessed using the competing risk method. Median progression-free survival (PFS) and overall survival (OS) were calculated from start of chemotherapy using the Kaplan-Meier method. Of the 386 patients diagnosed with mTNBC, 72% started a first-line and 38% a second-line of chemotherapy. At start of first- and second-line chemotherapy, 29% and 25% had de novo mTNBC, 49% and 57% bone metastases, 66% and 71% visceral metastases and 9% and 15% central nervous system metastases. First- and second-line chemotherapy included capecitabine in respectively 32% and 34%, taxanes in 25% and 27%, other single-agent chemotherapy in 6% and 17%, an AC-containing regimens in 14% and 5% and other combination-chemotherapy in 23% and 17% of patients. Median PFS and OS were 5.9 and 11.7 months from starting first-line and 3.8 and 8.7 months from starting second-line chemotherapy. In real-world clinical practice, first- and second-line chemotherapy for mTNBC included most often the single-agent chemotherapies capecitabine and taxanes. The prognosis of patients with mTNBC is poor, with a median survival of less than a year from start of first-line chemotherapy.

Pretreatment Hemoglobin Levels and Platelet-to-Lymphocyte Ratio Predict Survival Benefit from Pembrolizumab in Advanced Urothelial Carcinoma.

Several prognostic risk factors have been recognized when using cisplatin-based conventional chemotherapy for the treatment of advanced urothelial carcinoma (UC); these include performance status (PS), liver metastasis, hemoglobin (Hb) levels, time from prior chemotherapy (TFPC), and other systemic inflammation scores including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). However, the benefit of these indicators for predicting outcome of immune checkpoint inhibitors is not fully understood. Here, we investigated the predictive value of the indicators in patients who received pembrolizumab for the treatment of advanced UC. Seventy-five patients who received pembrolizumab treatment for advanced UC were included. The Karnofsky PS, liver metastasis, hemoglobin levels, TFPC, NLR, and PLR were analyzed, and their relationship with overall survival (OS) was determined. All factors were highlighted as significant prognostic indicators for OS in the univariate proportional regression analysis (p<0.05 for each). Multivariate analysis revealed that Karnofsky PS and liver metastasis were independent prognostic indicators for OS (p<0.01) but were applicable only for a small number of patients. Notably, the combined analysis with low Hb levels and high PLR was significantly associated with OS in patients who could gain less benefit from pembrolizumab at a median of 6.6 [95% confidence interval (CI)=4.2-9.0] versus 15.1 (95% CI=12.4-17.8) months (p=0.002). The combination of Hb levels and PLR may be a broadly applicable indicator for the outcome of pembrolizumab as second-line chemotherapy in patients with advanced UC.

Fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy for gemcitabine-refractory advanced pancreatic cancer: A systematic review and meta-analysis of randomized controlled trials.

Fluoropyrimidine-based regimens have been investigated as the second line chemotherapy in patients with advanced pancreatic cancer refractory to gemcitabine. We conducted this systematic review and meta-analysis to evaluate the efficacy and safety profile of fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in such patients. The databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts and ESMO Abstracts were systematically searched. Randomized controlled trials (RCTs) that compared fluoropyrimidine combination therapy versus fluoropyrimidine monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer were included. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate (ORR) and serious toxicities. Statistical analyses were performed by using Review Manager 5.3. Egger's test was performed to assess the statistical evidence of publication bias by using stata 12.0. A total of 1183 patients from six randomized controlled trials were included for this analysis. Fluoropyrimidine combination therapy increased ORR [RR 2.82 (1.83-4.33), p<0.00001] and PFS [HR 0.71 (0.62-0.82), p<0.00001], without significant heterogeneity. Fluoropyrimidine combination therapy improved OS [HR 0.82 (0.71-0.94), p = 0.006], with significant heterogeneity (I2 = 76%, p = 0.0009). The significant heterogeneity might have been caused by the different administration regimens and baseline characteristics. Peripheral neuropathy and diarrhea were more common in the regimens containing oxaliplatin and irinotecan, respectively. No publication bias was detected by Egger's tests. Compared with fluoropyrimidine monotherapy, fluoropyrimidine combination therapy had a higher response rate and longer PFS in patients with gemcitabine-refractory advanced pancreatic cancer. Fluoropyrimidine combination therapy could be recommended in the second line setting. However, due to concerns about toxicities, the dose intensities of chemotherapy drugs should be carefully considered in patients with weakness.

Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies.

The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.

Use, response and outcomes of second-line chemotherapy in patients with advanced biliary tract cancers.

First-line chemotherapy for advanced biliary tract cancers has been established as gemcitabine and cisplatin; however, there is currently no recognized standard second-line chemotherapy. The purpose of this study is to review and evaluate the outcomes of second-line chemotherapy for advanced biliary tract cancers. Patients who received chemotherapy for unresectable or metastatic biliary tract cancers at BC Cancer between August 2009 and December 2015 were retrospectively studied to identify second-line chemotherapy treatments used and to determine overall survival, time-to-treatment discontinuation and characteristics predicting for improved overall survival. Of 325 patients who received first-line chemotherapy for advanced biliary tract cancer, 90 (30%) received second-line chemotherapy. Median overall survival for patients who received only first-line chemotherapy was 9.5 months versus 17.3 months for patients who received second-line chemotherapy. Median time-to-treatment discontinuation for second-line chemotherapy was 2.0 months. Common drugs used in second-line chemotherapy treatments included capecitabine (30%), 5-fluorouracil and irinotecan (17%) and 5-fluorouracil monotherapy (15%). There was no difference in overall survival for patients who received single-agent second-line chemotherapy compared to doublet second-line chemotherapy. Patients who are fit enough to receive second-line chemotherapy may benefit in terms of overall survival and should be offered treatment with single-agent therapy. Capecitabine was the most common second-line chemotherapy treatment. The improved median overall survival for patients who received second-line chemotherapy may be impacted by independent patient-specific factors which are unknown at this time.

Association Between Peripheral Neuropathy Induced by Oxaliplatin at First-line Chemotherapy and Efficacy of Paclitaxel at Second-line Chemotherapy in Patients With Advanced Gastric Cancer.

Although peripheral neuropathy (PN) is a common adverse event in patients treated with oxaliplatin as first-line chemotherapy (1st-OX) for advanced gastric cancer, the effect of PN on the efficacy of paclitaxel at second-line chemotherapy (2nd-PTX) remains unclear. We investigated the association between PN induced by 1st-OX and efficacy of 2nd-PTX in patients with advanced gastric cancer (AGC). The study subjects were patients with AGC who received 1st-OX followed by 2nd-PTX at Gifu University Hospital between January 2015 and December 2019. Primary outcome was time to treatment failure (TTF) of 2nd-PTX. Secondary outcomes included overall survival (OS), response rate and adverse events during the period of 2nd-PTX. The association between incidence of grade ≥2 peripheral neuropathy (G2PN) and TTF or OS was also evaluated using Cox proportional hazards analysis. A total of 54 patients with AGC who received 1st-OX followed by 2nd-PTX were eligible. Incidence rates of G2PN at the start of 2nd-PTX was 20.3% (11/54). Median duration of TTF and OS were not significantly longer in patients with G2PN than in those without it (TTF: 4.7 months vs. 3.7 months, p=0.264, OS: 10.6 months vs. 8.5 months, p=0.706). Cox proportional hazards analysis indicated that there was no significant relationship between the incidence of G2PN and TTF, or between the incidence of G2PN and OS. However, development of grade ≥3 PN was significantly higher in patients with G2PN than in those without it (45.5% vs. 2.3%, p<0.001). G2PN induced by 1st-OX may not affect efficacy of 2nd-PTX in patients with AGC but could be a risk for grade ≥3 PN of 2nd-PTX.

MO23-3 Benefit of second-line chemotherapy in patients with advanced biliary tract cancer: A propensity score analysis

In advanced biliary tract cancer (BTC), combination of cisplatin and gemcitabine is recognized as the standard first-line chemotherapy regimen. Recently, FOLFOX regimen was tested in prospective randomized trial, ABC-06, and revealed to be beneficial as second-line therapy. However, there is no available data regarding the benefit of the treatment beyond first-line in Thai patients. This study aims to evaluate the efficacy of subsequent-line therapy in Advanced BTC.

Second-line therapy in testicular germ cell tumours: results from a tertiary cancer care centre in India.

BackgroundMalignant testicular neoplasms constitute about 1% of all cancers in males. This is one of the most common tumours in adolescents and young adult males. After the introduction of cisplatin-based chemotherapy, the survival of germ cell tumour patients, even those with poor prognostic risk factors, has significantly improved over the years. Second-line chemotherapy in patients who have progressed over the first-line cisplatin-based chemotherapy has shown convincing 5 years of overall survival (OS).MethodologyThis study is a retrospective analysis of testicular cancer patients from 2014 to 2020 who have received salvage chemotherapy treatment at Tata Memorial Centre. Patient demographics, tumour characteristics and treatment details were recorded in a specific format, and progression-free survival and OS were analysed along with response to therapy.ResultsA total of 46 testicular cancer patients from 2014 to 2020, who received second-line chemotherapy, were analysed from the database maintained at our hospital. The median age at diagnosis was 29.5 (18–60) years. Most of the patients (30, 65.2%) presented with lung metastasis and 11 (23.9%) patients with liver metastasis. Most of the patients (21, 45.6%) received vinblastine, ifosfamide and cisplatin, whereas 13 (28.2%) patients received paclitaxel, ifosfamide and cisplatin regimen and 7 (15.2%) patients received GemOx regimen as the second-line chemotherapy. Median OS was observed to be 33.97 months and median progression-free survival was 29.01 months.ConclusionSecond-line chemotherapy in testicular germ cell tumours can result in long-term disease control and all patients who are fit to tolerate second-line therapy should be offered it. Patients with relapsed seminoma did better than relapsed non-seminomatous germ cell tumours.

Abstract No. 243 Treatment Timing and Overall Survival of Liver-Dominant Metastatic Colorectal Cancer Patients Treated with Glass Transarterial Radioembolization: Analyses from the EPOCH Trial

The EPOCH trial investigated the potential benefit of adding transarterial radioembolization (TARE) with yttrium-90 glass microspheres to second-line chemotherapy in patients with liver-dominant metastatic colorectal cancer (mCRC). Post-hoc analyses evaluated the effect of TARE treatment day post calibration on clinical and safety outcomes.

Effectiveness of eribulin as first-line or second-line chemotherapy for HER2-negative hormone-resistant advanced or metastatic breast cancer: findings from the multi-institutional, prospective, observational KBCRN A001: E-SPEC study.

The optimal positioning of eribulin treatment remains unclear. This study aimed to investigate the effectiveness of eribulin administration as first- and second-line chemotherapy in patients with endocrine-resistant advanced or metastatic breast cancer (AMBC) in the real-world clinical setting. This multi-institutional prospective cohort study enrolled patients with triple-negative AMBC or estrogen receptor-positive AMBC refractory to at least one previous endocrine therapy. The overall survival (OS) from the start of first-line (OS1) and second-line chemotherapy (OS2) was assessed. Data analysis included real-world chemotherapy sequences of first- to third-line chemotherapy regimens. The adjusted hazard ratio (HR) with 95% confidence interval (CI) for treatment regimen comparison was calculated using a stratified proportional hazards model. Among 201 patients enrolled, 180 were included in the final analysis. Eribulin was administered as first- and second-line chemotherapy to 46 (26.6%) and 70 (47.9%) patients, respectively. Median OS1 and OS2 were 2.25 (95% CI 1.07-2.68) and 1.75 (95% CI, 1.28-2.45) years for first- and second-line eribulin, respectively. Oral 5-FU followed by eribulin had a numerically longer OS1 (2.84years) than the other sequences. Among patients who proceeded to second-line or later chemotherapy, the median OS1 for those treated with anthracycline or taxane as first- or second-line (n = 98) was 2.56years (95% CI 2.27-2.74), while it was 2.87years (95% CI 2.20-4.32) for those who avoided anthracycline and taxane as first- and second-line (n = 48) (adjusted HR, 1.20; 95% CI 0.70-2.06). In the exploratory analysis, OS1 was 2.55 (95% CI 2.14-2.75) and 2.91years (95% CI 2.61-4.32) for those aged < 65 and ≥ 65years, respectively (adjusted HR of ≥ 65, 0.91; 95% CI 0.56-1.46). Eribulin or oral 5-FU administration in first- and second-line chemotherapy without anthracycline/taxane was acceptable in the real-world setting. This study is registered with Clinical Trials.gov (NCT 02,551,263).

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for patients with metastatic colorectal cancer.

Fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab is the standard second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) who are refractory or intolerant to fluoropyrimidines and oxaliplatin. However, the benefits of incorporating fluoropyrimidines into second-line chemotherapy for patients with mCRC who are refractory to fluoropyrimidines are unknown. We retrospectively evaluated patients with mCRC who were administered irinotecan plus bevacizumab or FOLFIRI plus bevacizumab as second-line chemotherapy at a single institution from January 2010 to April 2020. We compared the efficacy and safety of irinotecan plus bevacizumab (IRI group) with those of FOLFIRI plus bevacizumab (FOLFIRI group). Of the 255 enrolled patients, 107 (IRI/FOLFIRI group, 31/76 patients) were eligible for analysis. After a median follow-up of 13.1months (range 1.2-48.4) and 14.3months (range 0.9-46.5) for the IRI and FOLFIRI groups, respectively, the median progression-free survival was 6.4months and 5.8months [adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI) 0.50-1.34, p = 0.44] and the median overall survival was 16.6months and 16.5months (aHR, 1.01; 95% CI 0.59-1.69; p = 0.97) in the IRI and FOLFIRI groups, respectively. All-grade nausea, stomatitis, neutropenia, thrombocytopenia, Grade 3/4 neutropenia, and febrile neutropenia occurred more frequently in the FOLFIRI group than in the IRI group. Our study suggests omitting fluorouracil from FOLFIRI plus bevacizumab as the second-line chemotherapy decreases adverse events without affecting the treatment efficacy in patients with mCRC who are refractory to fluoropyrimidines. Further randomized prospective studies are warranted to validate our result.

Radioembolization with chemotherapy for liver-dominant colorectal cancer: Time to subsequent treatment and quality of life in the EPOCH trial.

114 Background: The primary objective of the EPOCH trial evaluated potential benefit of adding second-line transarterial radioembolization (TARE) with yttrium-90 glass microspheres to chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Secondary endpoints included time to deterioration of quality of life (TTDQoL). Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial. TTDQoL was assessed using the Functional Assessment of Cancer Therapy-colorectal (FACT-c) questionnaire and defined as the time from randomization to the change from baseline in FACT-c total score ≤ -7 points or date of death and was estimated using Kaplan-Meier analysis. Time to subsequent therapy was defined as the time from randomization to the start of subsequent therapy and was estimated using Kaplan-Meier analysis. Restricted mean survival time (RMST) analysis was used to estimate the area under Kaplan-Meier curves (AUC) for progression-free survival (PFS), hepatic PFS (hPFS), and TTDQoL, and the difference in AUC estimates between the two arms were assessed. The use of TheraSphere in the USA in the trial was under Investigational Device Exemption from FDA. Results: The EPOCH trial included 428 patients. Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p&lt;0.0001) were met in the EPOCH study. Median time to subsequent therapy in the TARE plus chemotherapy arm was 21.0 months, compared to 10.1 months in the chemotherapy only arm (HR = 0.49, 95% CI: 0.37, 0.67). TTDQoL before subsequent therapy was reported in 53.5% (115/215) patients in the TARE plus chemotherapy arm, compared to 43.7% of patients in the chemotherapy only arm (93/213). Median TTDQoL was 3.8 months in both the TARE plus chemotherapy arm and the chemotherapy alone arm (1-sided p=0.1513; HR = 0.86, 95% CI: 0.65, 1.14). AUC for PFS until 22.1 months was 9.4 months (95% CI: 8.4, 10.4) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.6, 8.1) for the chemotherapy only arm (1-sided p=0.0008). AUC for hPFS until 22.1 months was 10.3 months (95% CI: 9.2, 11.3) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.7, 8.2) for the chemotherapy only arm (1-sided p&lt;0.0001). AUC for TTDQoL until 18.5 months was 6.6 (95% CI: 5.6, 7.6) for the TARE plus chemotherapy arm, compared to 5.5 (95% CI: 4.4, 6.5) for the chemotherapy only arm (1-sided p=0.0663). Conclusions: These results suggest that the addition of TARE to second-line chemotherapy in patients with liver-dominant mCRC extended PFS, hPFS, and time to subsequent treatment without compromising quality of life. Clinical trial information: NCT01483027.

A Precision Clinical-Omics Approach in Predicting Therapeutic Response to Pancreatic Cancer

Background: Pancreatic ductal adenocarcinoma is one of the most aggressive solid tumours. Despite numerous advances in surgical techniques, survival has remained largely unchanged over the last decade. Pancreatic cancer is thus considered a ‘systemic disease’ where chemotherapy plays a pivotal role in both the pre- and post-surgery setting. Tools that can predict the most effective chemotherapeutic regimens for patients are urgently needed to improve survival by optimising biological effects while minimising side effects, thereby not comprising their fitness for surgery. The aim of the study was to characterise the proteome of patient derived pancreatic cancer organoids to identify biomarkers predictive of chemotherapeutic sensitivity. Method: Using quantitative mass spectrometry we performed deep proteomic profiling of patient derived pancreatic cancer organoids with matched primary tumour tissue, and performed high-throughput combinatorial drug screening on organoid lines. Results: We demonstrated that common pancreatic cancer characteristics were conserved in organoids derived from different patients, and through comparative analysis between organoids revealed individual diversity that correlated with patient specific features. By correlating personalized organoid proteomes with their matched drug sensitivity profiles derived using high-throughput combinatorial drug screening, we identified protein biomarkers that correlated with therapeutic response to both standard of care and other novel therapeutics. Candidate biomarkers were verified by immunohistochemistry of organoids, with further validation to be performed in an interventional trial using organoids to predict second-line chemotherapy in patients with metastatic disease. Conclusions: We present the integration of deep proteomic profiling with a patient derived organoid platform for therapeutic biomarker discovery in pancreatic cancer.

The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective study.

BackgroundDespite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. MethodsWe reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020.ResultsAmong 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57–62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5–8.6 months) and 4.5 months (95% CI, 2.7–6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS.ConclusionThe survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.