Second-line therapies in PBC-related cirrhosis: balancing efficacy and safety

Comparative 10-year atherosclerotic cardiovascular disease risk in Ethiopian HIV patients on first-line versus second-line combined antiretroviral therapy.

This study reports on factors predicting response to second-line endocrine therapy in 250 patients with breast cancer for which they were assessable for response by the International Union Against Cancer (UICC) criteria. Clinical details relating to first-line endocrine therapy were available for all patients. We have not included in this study patients who received first-line endocrine therapy but did not or have not yet proceeded to second-line hormone therapy--e.g. died from rapidly progressive disease, started chemotherapy for rapidly progressive disease, or remained in long-term remission on first-line endocrine therapy. One hundred and fifty nine patients (72%) achieved remission (objective response and static disease [OR + SD]) on first-line endocrine therapy with a median duration of 19 months. For second-line endocrine therapy the remission rate was 53% (132/225) with a median duration of 15 months. Tumour grade and oestrogen receptor status of the primary tumour were shown to be independent predictors of response to second-line endocrine therapy while response to first-line endocrine therapy was a predictor of the duration of response to second-line endocrine therapy. In the sub-group of patients who showed OR or SD to both first and second-line therapies, there was no correlation between the time to progression (TTP) on first and second-line therapies.

Outcomes and Health Resource Utilization Among Second-Line Therapies for Immune Thrombocytopenia: A Provincial Retrospective Cohort Study

Introduction: Platinum-based chemotherapy was compared to single-agent pembrolizumab in advanced non-small cell lung cancer (NSCLC) with PDL1 > 50% in KEYNOTE-024. In this trial, it was found that patients who received single-agent pembrolizumab had improved progression-free survival in addition to overall survival (OS). Based on KEYNOTE-024, only 53% of patients treated originally with pembrolizumab received second-line anticancer systemic therapy with an OS of 26.3 months. Based on these results, the objective of this study was to characterize real-world NSCLC patients who received second-line therapy after single-agent pembrolizumab. Methods: This was a retrospective cohort study considering stage IV NSCLC patients diagnosed with BC Cancer between 2018 and 2021 with PD-L1 ≥ 50% who received first-line single agent pembrolizumab. Patient demographics, cancer history, treatment administered, and survival were collected retrospectively. Descriptive statistics were produced. OS was calculated using Kaplan–Meier curves and compared using the log rank test. A multivariate model evaluated characteristics associated with the receipt of second-line therapy. Results: A total of 718 patients were diagnosed with Stage IV NSCLC and received at least one cycle of pembrolizumab. The median duration of treatment was 4.4 months, and the follow-up duration was 16.0 months. There were 567 (79%) patients who had disease progression, of whom 21% received second-line systemic therapy. Within the subset of patients with disease progression, the median duration of treatment was 3.0 months. It would be found that patients who received second-line therapy had better baseline ECOG performance status, were younger at diagnosis, and had a longer duration of pembrolizumab. Within the full population, the OS from the treatment initiation date was 14.0 months. OS was 5.6 months in patients who did not receive additional therapy after progression and 22.2 months in patients who received subsequent therapy. Baseline ECOG performance status was associated with improved OS in multivariate analysis. Conclusion: Based on this real-world Canadian population, 21% of patients received second-line systemic therapy, despite second-line therapy being associated with prolonged survival. In this real-world population, we found that 60% fewer patients received second-line systemic therapy when compared to KEYNOTE-024. Although differences always exist when comparing a clinical and non-clinical trial population, our findings suggest undertreating stage IV NSCLC patients.

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer

Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.

Some studies suggest that blood pressure (BP)-lowering effects of commonly used antihypertensive drugs differ among ethnic groups. However, differences in the response to second-line therapy have not been studied extensively. In the BP-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA), BP levels of European (n = 4,368), African (203), and South-Asian- (132) origin patients on unchanged monotherapy (atenolol or amlodipine) and/or on second-line therapy (added thiazide or perindopril) were compared. Interaction between ethnicity and BP responses (defined as end BP minus start of therapy BP) to both first- and second-line therapies were assessed in regression models after accounting for age, sex, and several other potential confounders. BP response to atenolol and amlodipine monotherapy differed among the three ethnic groups (interaction test P = 0.05). Among those allocated atenolol monotherapy, black patients were significantly less responsive (mean systolic BP (SBP) difference +1.7 (95% confidence interval: -1.1 to 4.6) mm Hg) compared to white patients (referent). In contrast, BP response to amlodipine monotherapy did not differ significantly by ethnic group. BP responses to the addition of second-line therapy also differed significantly by ethnic group (interaction test P = 0.004). On adding a diuretic to atenolol, BP lowering was similar among blacks and South-Asians as compared to whites (referent). However, on addition of perindopril to amlodipine, BP responses differed significantly: compared to whites (SBP difference -1.7 (-2.8 to -0.7) mm Hg), black patients had a lesser response (SBP difference 0.8 (-2.5 to 4.2) mm Hg) and South-Asians had a greater response (SBP difference -6.2 (-10.2 to -2.2) mm Hg). We found important differences in BP responses among ethnic groups to both first- and second-line antihypertensive therapies.

To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second-line hormonal therapy for advanced hormone-refractory prostate cancer (HRPC). The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second-line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first-line hormonal therapy, which failed. The effect of the second-line therapy was evaluated by serum prostate-specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second-line therapy. On initiating second-line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1-13) months. During the observation period there were no severe side-effects from the second-line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first-line therapy had a significantly higher incidence of PSA response to second-line therapy, despite no significant effect of other factors examined on the PSA response to second-line therapy. Furthermore, the cause-specific survival in responders to second-line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second-line therapy, could be used as independent predictors of cause-specific survival. MAB using flutamide as second-line hormonal therapy can give a comparatively favourable PSA response with no severe side-effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first-line therapy.

6131 Background: Second-line therapy for patients with pancreatic cancer who have failed gemcitabine (GEM) based chemotherapy has been poorly studied. Limited clinical data suggest some survival benefit for second-line treatment; however, there is no second-line regimen that can be considered standard of care. This retrospective study reports the patterns of care and outcomes for second-line pancreatic cancer therapy among patients previously treated with GEM. Methods: Electronic medical records (iKnowMed) of 27 outpatient community cancer centers were reviewed. Pancreatic cancer patients with documented first-line GEM-based therapy during June 2006 to March 2009 were identified and followed through October 2009 or death. Chemotherapy and survival patterns were evaluated. Patients were excluded if there was history of clinical trial and/or insufficient data. Overall survival (OS) was calculated from date of diagnosis to death. Results: 368 out of 432 patients did not receive therapy beyond first-line (median age 66 years, 63% male); 64 out of 432 (15%) patients received second-line treatment (median age 67 years, 50% male). The most common second-line treatments reported were: capecitabine (CAP) or 5-FU (36%), oxaliplatin + CAP or 5-FU (23%), GEM + erlotinib (9%), other GEM combinations (17%) and other (15%). The median OS for patients receiving second-line therapy versus best supportive care was 435 weeks vs. 207 weeks (p < 0.0001; HR 1.66 [1.33-2.09]). Conclusions: The lack of use of and wide variation in second-line chemotherapy confirm that there is no standard alternative to supportive care. The benefit from second-line therapy is uncertain as, in the community setting, this patient population is highly selected. Further evaluation to determine patient characteristics and second-line therapy options to optimize survival benefit is warranted. No significant financial relationships to disclose.

P778 Effectiveness and safety of a second-line rescue therapy for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study)

248 Background: Gemcitabine (GEM) and GEM-containing combination chemotherapy have been established as standard first-line therapies for advanced pancreatic carcinoma (APC). In the GEST study, a phase III clinical trial that compared the results for GEM, S-1, and GEM+S-1 therapies, there was no significant difference between overall survival (OS) for GEM and GEM+S-1; S-1 and GEM had similar efficacies as first-line treatment for APC. Therefore, S-1 is expected to be used as first-line therapy. In our study, we have evaluated the efficacy and outcomes of second-line GEM therapy after S-1 therapy failure in APC. Methods: We retrospectively examined the data for 27 patients (pts) with APC refractory to first-line S-1 therapy. All the pts had undergone second-line GEM therapy during October 2000–February 2009 at National Cancer Center Hospital after first-line S-1 therapy. Tumor responses were analyzed using Response Evaluation Criteria in Solid Tumors. The Kaplan-Meier method was used to evaluate tumor progression and survival. Results: The Eastern Cooperative Oncology Group Performance Status was 0 or 1. The male:female ratio was 16:11 and median age was 62 years (range, 42–75 years). Four pts (14%) exhibited a partial response to second-line GEM therapy, 11 (40%) showed stable disease, and 12 (44%) showed progressive disease. Grade 3 adverse events for second-line GEM therapy were neutropenia in 2 pts and upper gastrointestinal hemorrhage in 1 pt. Grade 4 adverse events were not observed. The median progression-free survival was 77 days (95% confidence interval, 33–121 days) and the median OS after second-line GEM therapy was 240 days (95% confidence interval, 156–324 days). Conclusions: Although this study had a small sample population and retrospective design, the results indicate that GEM has good antitumor activity with tolerable toxicity. Second-line GEM therapy was found to be effective after first-line S-1 therapy failure in APC.

O3-004 - Efficacy of Gemcitabine as Second-Line Therapy after Failure of S-1 Therapy for Metastatic Pancreatic Carcinoma

Clinical Benefits of Achieving Deep Remission to Second-Line Therapy in Patients with Relapse/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL) - a Real-World Study

Digoxin has been an effective treatment for fetal supraventricular tachycardia (SVT), but second-line therapy remains more controversial. Thirty-seven cases of fetal SVT were identified that received digoxin as first-line therapy. Seventeen fetuses (46%) converted to and maintained normal sinus rhythm. Flecainide was used in 13/15 patients requiring second-line therapy; 12/13 (92%) converted to sinus rhythm. Of seven hydropic fetuses, five required second-line therapy and were then successfully converted with flecainide. The improved efficacy of flecainide was statistically significant with a p value <0.01. Complete follow-up was available in 13 digoxin-treated and in 12 second-line therapy infants. Prolonged or multiple drug therapy for postnatal arrhythmia management was required in 3/13 (23%) patients in the digoxin group and in 8/12 (67%) patients requiring second-line therapy. This demonstrated a correlation between the need for second-line fetal therapy and more complex postnatal management with a p value of 0.003. Digoxin remains an effective first-line therapy in the treatment of fetal SVT. Flecainide is an effective second-line therapy, especially in the face of fetal hydrops. Use of second-line therapy in fetal SVT is a predictor of complex postnatal course, and these patients should be followed more closely.

ObjectiveThe objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.DesignA randomised, double-blind,...