Previous Lines Of Chemotherapy Research Articles

The Incidence and Associated Risk Factors in Central Venous Catheter Associated Infectious Complications within the Autologous Stem Cell Transplant Population of Eastern Health

Background: Central venous catheters (CVCs) carry a risk of infectious complication with associated morbidity and mortality. Hematologic malignancies are a known independent risk factor for these complications. Patients undergoing hematopoietic stem cell transplant (HSCT) are at increased infectious risk with an incidence of 24.7-31.3%. Proposed contributors to this risk are the underlying malignancy, extended neutropenia, and increased requirement for blood products. Existing cohort studies of HSCT patients have been unable to identifying consistent, modifiable risk factors to target with infection prevention and control initiatives. This single-centre retrospective cohort study examines an autologous stem cell transplant population to identifying risk factors associated with CVCs. Objectives:To determine the incidence and incidence rate per 1000 catheter-days within the autologous HSCT program at Eastern HealthTo identify protective and risk factors associated with CVCs in HSCT patientsDescribe the causative agents in CVC infectious complication identified by blood and catheter-tip culture results Methods: Charts of all adult patients with hematologic malignancy who underwent HSCT with CVC placement at Eastern Health between January 1, 2014 and March 1, 2020 were examined to determine which patients experienced any of a catheter-related bloodstream, tunneled-line or exit site infectious complication as defined by the Public Health Agency of Canada's surveillance definitions. Risk factors assessed included patient factors (age, malignancy, history of bacteremia, fungemia or radiation therapy), immunosuppressive factors (lines of chemotherapy, total 90 day corticosteroid burden, erythropoietin use, days to polymorphonuclear cells >500/µL), and CVC factors (line type, insertion site, antibiotic prophylaxis, heparin impregnation, training level of radiologist, days indwelling, thrombotic complication. Additional data captured included 90-day mortality, whether the CVC was terminated and the causative organism identified by blood or catheter-tip culture. Preliminary Results: The incidence of total infectious complications was 56.2% with an incidence of catheter-related bloodstream infection (CR-BSI) of 22.9%. The incidence rate for total infectious complications was 6.51 per 1000-catheter days, with a CR-BSI infectious rate of 2.65. Both incidence and incidence rate were below results found in other centres. In univariate analysis found single-line of chemotherapy (HR 0.114, p=0.001), use of Permacath (HR 0.03, p=0.002), right internal jugular placement (HR 0.048, p=0.006) to be protective for infectious complication. Multivariate analysis identified a history of bacteremia (OR 763.1, p=0.039) and total days CVC indwelling (OR 0.94, p=0.011) to be associated with CVC infectious complication. Conclusion: Modifiable risk factors associated with CVC infectious complication are choice of device and placement site. Risk factors such as multiple lines of previous chemotherapy or history of bloodstream infection signal need to increased observation for infection. Disclosures No relevant conflicts of interest to declare.

Tamoxifen use in recurrent ovarian cancer in a Chinese population: A 15 -year clinical experience in a tertiary referral center.

AimTo review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer.MethodsA retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression‐free survival. We also attempted to identify predictive markers for response.ResultsA total of 92 patients received tamoxifen during this 15‐year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0–85 months), with 24 patients receiving it for more than 12 months. Seventy‐six patients continued on tamoxifen for more than 2 months. In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression‐free survival was 5.3 months (95% confidence interval, 2.6–8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response.ConclusionPatients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.

CtDNA Concentration, MIKI67 Mutations and Hyper-Progressive Disease Related Gene Mutations Are Prognostic Markers for Camrelizumab and Apatinib Combined Multiline Treatment in Advanced NSCLC.

Immunotherapy by immune checkpoint inhibitors (ICIs) has showed outstanding efficacy in the treatment of advanced non-small cell lung cancer (NSCLC). The combination of immunotherapy with anti-angiogenic therapy exhibited enhanced efficacy in multiline treatment. However, the potential biomarkers for predicting and monitoring the therapeutic response of the combined therapy remain undefined. In this study, we performed a pilot study by prospectively recruiting 22 advanced NSCLC patients who failed to previous lines of chemotherapy, chemoradiotherapy, TKI therapy, surgery, or any combination of the therapies, and investigated the prognostic factors for patients who received anti-PD-1 (Camrelizumab) and anti-angiogenic (Apatinib) combined therapy. The objective response rate (ORR) assessed by an independent radiology review was 22.7%, and the median progression-free survival (PFS) was 5.25 months. We found that high concentration of circulating-free DNA (cfDNA) (HR = 27.75, P = 0.003), MIKI67 mutation (HR = 114.11, P = 0.009) and gene variations related to hyper-progressive disease (HPD) (HR = 36.85, P = 0.004) were independent risk factors and exhibited significant correlation with PFS. Circulating tumor DNA (ctDNA) mutational status was also a predicting indicator for PFS. In contrast, the blood tumor mutational burden (bTMB) could not stratify the clinical benefit in this combined therapy (HR = 0.81, P = 0.137). Furthermore, we found that the variant allele fraction (VAF) of mutations in ctDNA was sensitive indicators of therapeutic response and therefore can be used to monitor the tumor relief or progression. In conclusion, cfDNA concentration, MIKI67 mutations and HPD-related mutations were independent risk factors and PFS predictors for multiline combined anti-angiogenic/ICI combined therapy. ctDNA may be a novel monitoring biomarker for therapeutic response and predicting biomarker for prognosis in future combined therapy involving PD-1 blockade.

Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience.

Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010–2018) in two different centers. Fifty patients (median age 52.5 years, range 34–75) were included; the median number of previous chemotherapy lines was three (range 1–7) and the median number of previous surgeries was one (range 1–4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC > 0 subgroup (median OS 32.9 months (95% CI 21.6–44.2) vs. 4.8 months (95% CI n.a.–9.8), hazard ratio (HR) 4.21 (95% CI 2.07–8.60), p < 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease.

Survival and clinical outcomes of patients with ovarian cancer who were treated on phase 1 clinical trials.

Patients with ovarian cancer who are enrolled on phase 1 trials typically have platinum-resistant and heavily pretreated disease, with a poor prognosis. In the current study, the authors assessed prognostic factors and survival in women with recurrent ovarian cancer who were treated on phase 1 clinical trials. The authors performed a retrospective analysis of patients treated from 2008 through 2018 at the University of Colorado Cancer Center. Patient characteristics and treatment and toxicity-related survival data were assessed. Descriptive statistics and Cox proportional hazards models were used to identify risk factors associated with survival time. A total of 132 patients were treated on phase 1 clinical trials. Patients had a median age of 59 years (range, 33-88 years) with a median of 5.5 previous chemotherapy lines (range, 1-13 lines). Of the 132 patients, 53 (40%) were treated on multiple phase 1 trials with a median of 1 (range, 0-5) prior phase 1 trial. The overall response rate was 14.7%. The median overall survival was 11.3 months (95% CI, 9.1-13.4 months). Two patients died on trial due to progression of disease whereas no patients died of treatment-related toxicity. Independent risk factors found to be predictive of shorter survival were an elevated cancer antigen 125 (CA 125) level (hazard ratio [HR], 2.8; 95% CI, 1.6-5.2) and albumin <3.5 g/dL (HR, 2.5; 95% CI, 1.65-3.79). A body mass index >25 kg/m2 was predictive of longer survival (HR, 0.65; 95% CI, 0.44-0.96). In the current single-institution series, patients with heavily pretreated ovarian cancer who were treated on phase 1 clinical trials experienced a median overall survival of 11.3 months. When available, phase 1 clinical trials represent a reasonable treatment option for patients with heavily pretreated ovarian cancer with a preserved performance status.

Conditioning Regimens for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Stem Cell Transplantation: BEAM Versus High Dose ICE.

There are different drug combinations and conditioning regimens in lymphoma transplants. However, no randomized data is available to demonstrate the superiority of any regimen and the optimal choice is unknown. In this analysis, we compared the efficacy, toxicity and the survival outcomes of the BEAM and the high dose ICE (hdICE) conditioning regimens in relapsed NHL and relapsed/refractory Hodgkin Lymphoma patients undergoing auto-SCT. 83 patients with relapsed/refractory HL or relapsed NHL who were treated with Auto-SCT between 2006 and 2016, were analyzed retrospectively. 52 patients (62.7%) received BEAM, while 31 patients (37.3%) received hdICE. Between two groups there is no significant difference in age, gender, diagnosis, disease stage, chemosensitivity, ECOG performance status, time from diagnosis to transplant, salvage regimens and previous lines of chemotherapy. After a median of 59-month follow-up, PFS and OS rates of both groups were similar (5-year PFS was 51.6% in BEAM group, 48.8% in hdICE group, p = 0.71; 5-year OS was 58% in BEAM group, 54.8% in hdICE group, p = 0.93). The median neutrophil (11 vs. 10days, p = 0.06) and platelet engraftment (13 vs. 11days, p = 0.01) was faster and demand of transfusions were lesser in hdICE group (p = 0.03). However, severe renal toxicity was significantly higher in hdICE group in our study (p = 0.01). hdICE conditioning regimen may be used as an alternative to BEAM, with similar survival outcomes and toxicity profile, especially transplant centers that experience some difficulties in the availability of the carmustine.

Efficacy and safety of low-dose apatinib in ovarian cancer patients with platinum-resistance or platinum-refractoriness: A single-center retrospective study.

BackgroundThis study aimed to evaluate the efficacy and safety of apatinib with a low dose of 250 mg/d in the treatment of platinum‐resistant or platinum‐refractory ovarian cancer patients.MethodsPatients with platinum‐resistant or platinum‐refractory ovarian carcinoma treated with 250 mg/d apatinib in our institution from November 2016 to December 2017 were retrospectively reviewed. The tumor response and progression were evaluated according to the standard by incorporating the levels of CA125 and Response Evaluation Criteria in Solid Tumors 1.1. CTCAE 4.03 was used to evaluate adverse events (AEs).ResultsFifty‐two eligible patients were enrolled in per‐protocol (PP) analysis and 65 patients (including 13 lost to follow‐up) were included in the intention‐to‐treat (ITT) analysis. In PP analysis, 18 patients (34.6%) had partial response (PR), 22 patients (42.3%) had stable disease (SD), and the disease control rate (DCR) was 61.5%. Median progression‐free survival (PFS) was 4.0 months (95% CI, 2.83‐5.17 m), and median overall survival (OS) was 25.33 months (95% CI, 17.74‐32.92 m). The objective response rate and DCR for patients in ITT analysis were 27.7% and 49.2%, respectively. The top three treatment‐related AEs were hypertension, hand‐foot syndrome, and leukopenia. Eight patients (15.4%) in PP population had grade 3 treatment‐related AEs. Previous chemotherapy lines, number of recurrences, and AEs did not affect the efficacy of apatinib. Age older than 60 was associated with higher rates of disease control and prolonged PFS (P < .05).ConclusionApatinib 250 mg/d is a feasible treatment in platinum‐resistant or platinum‐refractory epithelial ovarian cancer (EOC) patients.

Gls-010, a novel anti-PD-1 mAb in Chinese patients with recurrent or metastatic cervical cancer: Results from a multicenter, open-label and single-arm phase II trial.

6032 Background: GLS-010 is a novel fully human anti-PD-1 mAb. Previous Phase I study exhibited favorable result of tolerance, preliminary efficacy and 240mg fixed dose q2w was selected as Recommended Phase II Dose (RP2D). This Phase II clinical trial is aimed to further evaluate the safety and anti-tumor activity of GLS-010 in patients with recurrent or metastatic cervical cancer. Methods: PD-L1 positive (combined positive score (CPS) ≥1) patients with recurrent or metastatic cervical cancer who had received one or more lines of chemotherapy were enrolled and received GLS-010 240mg every 2 weeks. Primary endpoint was the objective response rate (ORR) per RECIST 1.1, secondary endpoints included duration of response (DoR) and safety. Results: From May 16th 2019 to December 24th 2019, 44 pts were enrolled and treated in the study. As of December 24th 2019,the median line of prior systemic chemotherapy was 2(range: 1~4), and 59% (26/44) of pts had received ≥2 previous lines of chemotherapy. The median number of GLS-010 doses was 1.5(range: 1~4). 25 pts received response evaluation per investigator review. With a median follow-up of 2.9 months, 7 of 25 evaluable pts achieved a partial response (PR). The ORR was 28% (95% CI, 12.07-49.39), with 7 pts achieving a PR ( 3 of 7 confirmed), 3 pts achieving stable disease (SD) and 15 pts with progressive disease (PD), 1 of which was assessed as dissociated response with treatment ongoing. Median duration of response had not been reached yet. 33 of 44 patients (75%) experienced one or more treatment-related adverse events (TRAEs) per NCI CTCAE v4.03, most of which were grade 1 or 2. The most common TRAEs were Anaemia (15/44), and 73.3% of them were grade 1 or 2. The most common ≥grade 3 TRAE included Anaemia (4/44). As data cut off, only 1 pt discontinued treatment due to adverse event. Conclusions: GLS-010 showed impressive therapeutic activity and manageable safety profile in Chinese recurrent or metastatic cervical cancer patients. Current evidence support further development of GLS-010 in this and more indications. This trial is still ongoing, and we are looking forward to further results. Clinical trial information: NCT03972722.

Effect of anlotinib in advanced small cell lung cancer (SCLC) patients relapsed within three months after second-line treatment: A subgroup analysis from a randomized, double-blind phase II trial (ALTER 1202).

9063 Background: Anlotinib had significantly improved progress-free survival (PFS) and overall survival (OS) of advanced small cell lung cancer (SCLC) patients received at least two lines chemotherapy in the ALTER 1202 trial. Here, we reported the effect of anlotinib in advance SCLC patients relapsed within 3 months after second-line treatment. Methods: The ALTER 1202 was a randomized, double-blind phase 2 trial including patients with advanced SCLC that received at least two previous lines of chemotherapy. Eligible patients were randomized in a 2:1 ratio to receive either anlotinib or placebo until tumor progression or unacceptable toxicity. The subgroup analysis assessed the effect of anlotinib in patients relapsed within 3 months after second-line treatment. The primary outcome was PFS. The secondary outcomes were OS, objective response rate (ORR), disease control rate (DCR) and safety. This trial was registered with ClinicalTrials.gov, number NCT03059797. Results: In the ALTER1202 trial, 67 patients in anlotinib group and 34 patients in placebo group relapsed within 3 months after second-line treatment. Among them, the median PFS was 3.98 months (95% confidence interval [CI], 2.79 to 4.24) with anlotinib versus 0.72 months (95% CI, 0.69 to 0.82) with placebo (hazard ratio [HR], 0.14; 95% CI, 0.08 to 0.26; P &lt; 0.0001). Meanwhile, anlotinib significantly prolonged OS compared with placebo (7.29 months [95% CI, 6.51 to 10.51] versus 4.37 months [95% CI, 2.33 to 6.47]; HR, 0.42 [95% CI, 0.23 to 0.74]; P = 0.0059) in patients relapsed within 3 months after second-line treatment. ORR was 4.48% (3 PR) for anlotinib and 2.94% (1 PR) for placebo (P = 0.708). DCR was 73.13% for anlotinib and 11.76% for placebo (P &lt; 0.0001). The most common adverse events were hypertension (38.81%), anorexia (28.36%), fatigue (22.39%) and Elevation of alanine aminotransferase (17.91%). Conclusions: Anlotinib improved PFS and OS in advanced SCLC patients relapsed within 3 months after second-line treatment and was well tolerated.

Anlotinib in patients with recurrent advanced cervical cancer: A prospective single-arm, open-label, phase Ⅱ trial.

6034 Background: Anlotinib is a novel multi-target tyrosine kinase inhibitor that has previously shown clinical antitumor activity in various cancers, including the phase I study on female genital tumors. This phase II study (ChiCTR1800020116) aims to further evaluate the safety and efficacy of anlotinib, in those patients with recurrent advanced cervical cancer. Methods: Eligible patients were advanced cervical cancer who had received at least two previous lines of chemotherapy. Patients were given anlotinib (12 mg/day) from day 1 to day 14 in a 21-day cycle until disease progression or had unacceptable toxic effects. The primary endpoint of this study was objective response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Results: Between 2018 December and 2019 October, 41 patients (female) were enrolled. As of January 15, 2020, median follow-up duration, from randomization to data cutoff, was 2.6 months (range, 0.7-10.3). Therapeutic evaluation showed the ORR was 32.1% (95%CI, 13.7%-50.6%) and the median PFS was 3.9 months (95% CI, 1.3%-6.5%). The most frequently reported adverse events were lymphocyte count decreased, anemia, hand-foot syndrome, blood uric acid increased, blood creatinine increased, blood thyroid stimulating hormone increased. All frequently occurring AEs were grade 1 or 2. High grade AE was only observed in 1 patient with white blood cells urine positive of grade 3. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib showed a promising activity with an acceptable safety profile for patients with recurrent advanced cervical cancer. Clinical trial information: ChiCTR1800020116.

Olaparib maintenance monotherapy for non-germline BRCA1/2-mutated (non-gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase IIIb OPINION interim analysis.

6057 Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al. Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including those in the non-BRCAm subgroup. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et al. Lancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 previous lines of platinum-based chemotherapy, we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and had responded to platinum-based chemotherapy. Pts initiated maintenance olaparib tablets (300 mg bid) until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed PFS (modified RECIST 1.1). Secondary endpoints included PFS by homologous recombination repair deficiency (HRD; assessed with the Myriad myChoice HRD plus test; HRD+ve: score ≥42) and somatic BRCA mutation (sBRCAm) status. An interim analysis was planned after ~135 PFS events. Results: 279 pts were enrolled from 17 countries (mean age: 64 yrs); 94.3% were confirmed non-gBRCAm by local testing. At data cut-off (Nov 15, 2019), the median PFS was 9.2 months (95% confidence interval [CI]: 7.6–10.9 months), with 152 PFS events (54.5% maturity). The Table presents PFS outcomes by key subgroups. The median exposure to olaparib was 8.1 months. Grade ≥3 adverse events (AEs) occurred in 72 (26%) pts. 19% of pts reported serious AEs. No deaths related to AEs were reported. AEs led to dose interruption, dose reduction and treatment discontinuation in 39%, 15% and 7% of pts, respectively. Conclusions: Maintenance olaparib demonstrated activity in non-gBRCAm PSR OC pts. There were no new safety signals. Clinical trial information: NCT03402841. [Table: see text]

Correlation of longtime efficacy maintenance PARP inhibitor therapy with pre-treatment in a single-institution experience.

e18084 Background: The use of PARP inhibitors (Olaparib-Niraparib) has shown an important benefit in PFS in patients with relapsed ovarian cancer both with gBRCA and non-BRCA mutation. Methods: This was a single-institution, retrospective cohort study of 93 patients. Clinical data were obtained by the review of the electronic medical report. The 93 patients were treated with PARP Inhibitors(PARP-I) between Apr 2014 and Dic 2019. The patients were evaluated according to age, BRCA mutation, pretreatment with Trabectedin, Bevacizumab, last line of pretreatment with Platinum-Gemcitabine+Paclitaxel versus Caelyx-Oxaliplatin, number of previous lines of chemotherapy, residual disease before PARP-I. Statistical analysis of survival was performed with Kaplan-Meyer, univariate and multivariate analysis with Cox regression. Disease Free Survival (DFS) was evaluated from the start of PARP-I therapy while Overall Survival (OS) from the diagnosis. Results: Median age was 64 (42-90), patients with germinal mutation BRCA were 34 (36.6%), 58 without mutation and 1 patient without genetical analysis. 20 (21,5%) patients were pretreated with Trabectedin plus Pegylated Liposomal Doxorubicine (PLD), while 8 (8,6%) with Trabectedin-Bevacizumab, 26 (28%) patients were pretreated with Bevacizumab +/- Trabectedin. Before PARP-I patients more frequently were pretreated with 2-3 line 60, 64.5%): in the last line of pretreatment chemotherapy 47 (50,4%) patients received PLD+-Oxaliplatin versus Carboplatin-Taxol or Carboplatin-Gemcitabine. In 64% of the patients CTscan or ecography showed residual disease &gt; 1 cm before starting PARP-I treatment . Median follow-up was 17 months: 54 (58.1%) patients in PARP-I treatment relapsed, while 32 (34.1%) patients died. Multivariate analysis showed a significant association in the number of lines pretreatment: in more than 3 lines HR was 2.00 (CI 1.2-3.4, p = 0.012), according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286). Conclusions: The administration of PARP is important for OS immediately after 2° line chemotherapy in platinum sensitive patients Logrank p = 0.0065, with higher response not significant, about OS specially if following non-anemic PLD-Oxaliplatin therapy (p = 0,0849 Logrank) Also significant is OS according to residuum less or more 1 cm prior to start PARP therapy (logrank p = 0,0286) The doses and relative reductions in PARP-I did not change efficacy.

Efficacy and Safety of Anlotinib in Advanced Non-Small Cell Lung Cancer: A Real-World Study.

PurposeThe ALTER0303 trial showed that anlotinib, a novel antiangiogenic tyrosine kinase inhibitor, administered as third-line or further treatment prolonged progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). This retrospective study investigated the efficacy and safety of anlotinib in real-world settings.Patients and MethodsMedical records of patients with advanced NSCLC receiving anlotinib as third-line or further treatment were collected, and survival curves were derived using the Kaplan–Meier method. Univariate analysis was performed by log-rank testing. Cox regression analysis was used to evaluate the significance of factors obtained from the univariate analysis.ResultsFifty-two patients with advanced NSCLC were included. The objective response rate was 16%, and the disease control rate was 80%. The median PFS was 4.5 months (95% confidence interval [CI]: 3.6–5.4), and the median OS was 9 months (95% CI: 6.5–11.5). Univariate analysis revealed that the group of patients with longer PFS and OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, ≤2 distant metastases, no liver metastases, ≤3 previous treatment lines, and ≤2 previous chemotherapy lines. Cox regression analysis demonstrated that only patients with ECOG PS ≤1 or no liver metastases had longer PFS and OS. Grade 3 treatment-related adverse events were reported in 14% of the patients, but no life-threatening adverse events were reported.ConclusionAnlotinib was well tolerated and effective in patients with advanced NSCLC in real-world conditions. Patients with ECOG PS ≤1 or no liver metastases have longer PFS and OS.

Clinical Variables Associated with PSA Response to Lutetium-177-PSMA ([177Lu]-PSMA-617) Radionuclide Treatment in Men with Metastatic Castration-Resistant Prostate Cancer.

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan–Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or χ2/Fisher’s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of <0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline ≥20% and ≥50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline >20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the ‘real-life’ setting of heavily pretreated men with mCRPC.

Pazopanib and Oral Cyclophosphamide in Women With Platinum-Resistant or -Refractory Epithelial Ovarian Cancer.

PURPOSEWomen with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide.PATIENTS AND METHODSWomen with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity.RESULTSTwenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity.CONCLUSIONPazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

Abstract P4-10-08: Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC)

Abstract Objective: This post hoc analysis assessed predictors for OS in patients (pts) treated with eribulin using data from 2 phase 3 studies: EMBRACE and Study 301. Background: Eribulin is a nontaxane synthetic inhibitor of microtubule dynamics approved for use in locally advanced or metastatic breast cancer after two previous lines of chemotherapy. In EMBRACE, 508 pts were randomized to eribulin monotherapy and 254 pts to the treatment of physician’s choice (TPC). Median OS of pts in the eribulin arm was significantly better than the TPC arm but no significant difference was seen in progression-free survival (PFS) by independent review. Study 301 randomized 554 pts to eribulin and 548 pts to capecitabine; no significant difference was seen in PFS. Kashiwagi et al, PloS one, 2017, suggested that cells such as tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment may be a predictive marker of eribulin efficacy—pts with a high number of TILs had significantly longer PFS than pts with low TIL counts. Miyagawa et al, Clin Breast Cancer, 2018, found neutrophil-to-lymphocyte ratio to be significantly associated with longer PFS with eribulin. Our analysis focused on ALC, a peripheral immune parameter. Methods: Pts from EMBRACE with baseline ALCs were included in this analysis. The Kaplan-Meier method was used to estimate OS distribution. Interaction analysis of OS was performed between treatment and baseline ALCs to explore differential cutoff values. Hazard ratios (HR) were estimated from the stratified Cox proportional hazard model with the randomization stratification factors: HER2/neu status, prior capecitabine treatment, and geographical region. Multivariate analyses for baseline factors were performed using the Cox proportional hazard model to identify predictors and to confirm baseline ALC effect for OS. Similar methods were used to analyze associations between baseline ALC and OS in Study 301. Results: EMBRACE included 500 pts in the eribulin arm and 251 in the TPC arm with an evaluable baseline ALC. Pts with high baseline ALC consistently experienced greater eribulin benefit vs pts with low baseline ALC across cutoff values from 1300-1750/μL. The greatest difference was observed at the cutoff value of 1500/μL. Median OS was higher in pts with baseline ALC ≥1500/µL vs baseline ALC &amp;lt;1500/µL in the eribulin arm (15.6 vs 11.6 months) but not in the TPC arm (Table). The eribulin group showed prolonged OS compared with the TPC group in pts with ALC ≥1500/µL (HR 0.586; 95% CI: 0.437-0.784; P&amp;lt;0.001). There was no significant difference by treatment for ALC &amp;lt;1500/µL (HR 1.002; 95% CI: 0.800-1.253; P=0.989). Study 301 included 553 pts on eribulin and 547 pts on capecitabine. Similar results were observed in the eribulin arm, median OS was higher in pts with baseline ALC ≥1500/µL vs pts with baseline ALC &amp;lt;1500/µL (19.6 vs 14.6 months). There was a treatment effect favoring eribulin vs capecitabine at ALC ≥1500/µL but not at ALC &amp;lt;1500/µL. Conclusion: ALC at baseline may potentially be an independent predictor for longer OS in pts treated with eribulin. This hypothesis-generating study speculates that baseline ALC may be useful in the selection of pts to be treated with eribulin. Table. Multivariate analysis of OS identified the following predictors for OS in the eribulin group: prior capecitabine, ECOG PS, HR status, number of organs involved, refractory to taxanes, and baseline ALCStudyBaseline ALCArmPatients, nMedian OS (months)HR (95% CI)EMBRACEALC ≥1500/µLEribulin19915.60.586 (0.437-0.784)TPC9211.4ALC &amp;lt;1500/µLEribulin30111.61.002 (0.800-1.253)TPC15910.3Study 301ALC ≥1500/µLEribulin23319.60.811 (0.662-0.993)Capecitabine26916.0ALC &amp;lt;1500/µLEribulin32014.60.907 (0.758-1.084)Capecitabine27812.5ALC, absolute lymphocyte count; CI, confidence interval; HR, hazard ratio; OS, overall survival; TPC, treatment of physician’s choice. Citation Format: Javier Cortes, Jose Manuel Perez-Garcia, Kenichi Nomoto, Karenza Alexis, Kenichi Saito, Yuta Yoshimura, Kenzo Muramoto, Yasuo Miyoshi. Absolute lymphocyte count (ALC) is a predictor of eribulin benefit in advanced or metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-08.

Abstract P4-10-25: Pretreatment serum metabolome predicts PFS in first-line trastuzumab-treated metastatic breast cancer

Abstract Background: Cancer cells have altered metabolism, which contributes to their ability to proliferate, survive in unusual microenvironments, and invade other tissues. Measuring the complete set of metabolites in an individual (i.e. the metabolome) provides a functional readout for cellular pathways. Further, changes in the metabolome can be correlated with disease status, prognosis and progression. Using a metabolomics platform and machine learning algorithms, biomarker signatures can be identified to predict response to therapy. Metabolite analysis of pretreatment plasma has shown promise for predicting response in a small retrospective study of the CDK 4/6 inhibitors palbociclib and ribociclib in hormone receptor-positive metastatic breast cancer (Zhang B et al, ASCO 2019 Abstr 3043). HER2-positive metastatic breast cancer patients have significant heterogeneity in response and progression-free survival (PFS) to HER2-targeted therapy. Here we retrospectively evaluated the pretreatment serum metabolome for association with PFS in a cohort of trastuzumab-treated metastatic breast cancer patients from a single institution. Methods: Pretreatment serum from 26 HER2-positive trastuzumab-naive metastatic breast cancer patients who were treated with first-line trastuzumab and chemotherapy were included in this exploratory analysis. Metabolites were extracted from previously frozen serum (1 mL) using ice-cold methanol and chloroform. The resulting metabolites were isolated and quantified using an unbiased, non-destructive, nuclear magnetic resonance (NMR)-based profiling platform (Olaris, Inc., Cambridge, MA). The serum was analyzed via 1D 1H NMR and 2D 13C-1H heteronuclear single quantum coherence spectroscopy (HSQC) using customized non-uniform sampling (NUS) techniques and processed with proprietary Olaris software. Supervised and unsupervised machine learning algorithms were used to identify patients with shorter and longer PFS to trastuzumab-based therapy. Results: The median PFS for this cohort was 301 days. Patients were subdivided into early progressors (PFS &amp;lt; 301 days) and late progressors (PFS ≥ 301 days). 23 metabolite resonance levels were statistically different between the two groups (KW test p&amp;lt;0.05, 11 metabolites expected by chance). Using advanced machine learning we constructed a model based on 5 metabolite resonances that showed significant discriminatory ability with an AUC of 0.964 using receiver-operating curve (ROC) analysis. 21 of the 26 patients received trastuzumab and chemotherapy as a first-line therapy, while the remaining 5 patients received first-line trastuzumab with subsequent chemotherapy, after 1 or more lines of previous chemotherapy for metastatic disease. We repeated our analysis using only the first-line therapy subgroup and identified a partially overlapping set of metabolite resonances that could nearly perfectly discriminate early and late progressors with an AUC of 0.973. Further efforts are underway to confirm the identity of these metabolites. Conclusions: Metabolic profiling of pretreatment serum using NMR was successful in identifying a biomarker signature that predicted PFS to trastuzumab in HER2-positive metastatic breast cancer. Expanded metabolome analysis is warranted in larger cohorts and clinical trials to confirm that this serum biomarker signature predicts PFS to trastuzumab therapy, particularly in the first-line setting. Further, by identifying the metabolites and metabolic pathways that differ between early and late progressors, it may be possible to identify novel targets and/or suggest combination treatments in the HER2-positive metastatic breast cancer setting. Citation Format: Elizabeth O'Day, Kim Leitzel, Suhail M Ali, Bo Zhang, Chen Dong, Haiwei Gu, Xiajian Shi, Joseph J Drabick, Leah Cream, Monali Vasekar, Hyma V Polimera, Vinod Nagabhairu, Prashanth Moku, Ashok Maddukuri, Harry Menon, Neha Pancholy, Walter P Carney, Wolfgang Koestler, Allan Lipton. Pretreatment serum metabolome predicts PFS in first-line trastuzumab-treated metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-25.

The Effect of Skipped Collections on Stem Cell Product Yields in Difficult to Mobilize Multiple Myeloma Patients

Multiple Myeloma (MM) is incurable disease and autologous stem cell transplant (ASCT) remains an important modality of treatment. Current mobilization strategies result in mobilization failure rates as high as 5-10% among patients with MM1. According to our institutes policies, patients are prepared for stem cell collection with a Cytoxan based mobilization regimen plus GCSF/Mozobil (chemo-mobilization), or GCSF/Mozobil (growth factor) alone. Most often, patients undergoing chemo-mobilization and growth factor-based mobilization achieve adequate CD34 count in peripheral blood by day 14 and 5, respectively. Apheresis is performed after adequate CD34 is measured in the peripheral blood. We identified 18 MM patients, during 2016-2019, who did not achieve adequate CD34 count and were classified as difficult mobilizers. In this cohort, the median age was 57 years, 84% had diffuse marrow involvement and/or multiple lytic lesions, 39% had received an alkylating agent and 28% had received at least two previous lines of chemotherapy. 13 patients who were chemo-mobilized, did not achieve adequate CD34 yield, after 5 days of continuous apheresis. Similarly, 5 patients in GCSF/Mozobil arm did not achieve adequate CD34 yield after 5 days of continuous apheresis. Hence, we gave them planned 48 hours break from further GCSF or Mozobil exposure. After the break, we resumed GCSF/Mozobil for 1 day, and subsequently we noticed significant rise in peripheral blood CD34 count in some of the patients. We achieved a median collection of 3.98 CD34+ cell/kg in these difficult mobilizers. We compared collection to the easy mobilizers during the same time period and the median collection for easy mobilizers was 4.48 CD34+ cell/kg. The skipped day strategy led to adequate yields for ASCT in 100% of the difficult to mobilize patients. One possible explanation for the higher number of cells collected after the skipped day is that continuous exposure to GCSF leads to tachyphylaxis of GCSF receptors, and the break relieves this phenomenon, allowing better collection after the break. Further studies exploring this planned break strategy needs to be conducted in so called difficult mobilizer patient group.

Clinical and molecular factors for selection of nivolumab or irinotecan as third-line treatment for advanced gastric cancer.

Background:The use of nivolumab or irinotecan as the third-line treatment for patients with advanced gastric cancer (AGC) remains controversial.Methods:This study analyzed patients with AGC treated with nivolumab or irinotecan (nivolumab group or irinotecan group, respectively) from May 2016 to April 2019 following two or more previous lines of chemotherapy. Univariate survival analysis was conducted to identify the clinical and molecular factors associated with progression-free survival (PFS).Results:A total of 156 patients (74 treated with nivolumab and 82 treated with irinotecan) were analyzed. The median PFS was 1.9 months in both treatment groups. The median overall survival (OS) was 7.2 and 6.2 months in the nivolumab and irinotecan groups, respectively. Eastern Cooperative Oncology Group performance status of 1 or more, liver metastasis, a large tumor size at baseline, and HER2-positive status were associated with a worse PFS in the nivolumab group compared with the irinotecan group. The nivolumab group showed a significantly longer PFS (median 3.1 versus 2.0 months) and OS (median 12.9 versus 7.8 months) than the irinotecan group in patients with 0 or 1 of these factors, whereas the irinotecan group showed a significantly longer PFS (median 1.0 versus 1.8 months) and a trend of longer OS (median 3.9 versus 6.1 months) in patients with ⩾2 of these factors.Conclusions:Some clinical and molecular factors were associated with outcomes following nivolumab or irinotecan as the third- or later-line treatment in patients with AGC. These factors must be considered while selecting an optimal treatment option.

Eribulin monotherapy in heavily pretreated metastatic breast cancer patients in real life.

Our retrospective, single-center study aimed at evaluating the efficacy and safety of eribulin in heavily pretreated metastatic breast cancer (MBC) in routine clinical practice. Twenty-eight patients treated with eribulin for MBC between May 2014 and November 2017 were included in our study. Clinical and biological assessment of toxicity was controlled at each visit. Tumor response was evaluated every three cycles of treatment. Median age at eribulin treatment was 52.5-year. Tumors were hormone receptor positive (71.4%), HER2-positive (10.7%), and triple negative (TN) (25%). Most of the patients (92.8%) presented with visceral metastases, mainly in the lymph nodes (57.1%) and liver (53.6%). Median previous metastatic chemotherapy line was 4 [1-7]. Median number of metastatic sites were 3 (1-4). Median number of eribulin cycles was 4. At the end of follow-up period, 36% of the patients were still alive. Eighteen patients died due to disease progression. The objective response rate was 21.5% with a 42.9% clinical benefit rate. Median progression-free survival and overall survival (OS) were 4 (95% CI: 2.7-5.2) and 14 (95% CI: 11.8-16.1) months, respectively. Treatment was well tolerated. None of the patients discontinued eribulin treatment due to toxicity. The most commonly reported toxicities were asthenia (71.4%), peripheral neuropathy (67.9%), and neutropenia (46.4%). Eribulin is an effective new treatment option in heavily pretreated MBC, with a manageable toxicity profile. Our results confirm that treatment with eribulin is feasible and safe in real-world patients.