Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience

Abstract

The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≧ 79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.     

Imipenem/Cilastatin Monotherapy as Salvage Treatment in Febrile Neutropenic Patients

Abstract

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twentyfive out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47 %) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash.

In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.     

A retrospective evaluation of second-line chemotherapy response in hormone-refractory prostate carcinoma: second line taxane-based therapy after first-line epothilone-B analog ixabepilone (BMS-247550) therapy

BACKGROUND: Epothilones and taxanes interfere with microtubule function. Ixabepilone, which is an epothilone-B analog, has activity against taxane-resistant cell lines and as first-line therapy for men with hormone-refractory prostate carcinoma (HRPC). Clinical cross-resistance of ixabepilone and taxanes in HRPC is unknown. METHODS: Records were evaluated retrospectively from patients with HRPC who were treated on a randomized Phase II trial of ixabepilone with or without estramustine and who subsequently received taxane chemotherapy. Posttherapy declines in prostate-specific antigen (PSA) levels and time to PSA progression were defined by consensus criteria. The median survival was evaluated by using the Kaplan-Meier method. RESULTS: Forty-nine patients who received ixabepilone with estramustine (28 patients) or without estramustine (21 patients) subsequently received second-line taxane therapy. Second-line PSA declines > or = 50% were achieved by 51% of patients (95% confidence interval [95% CI], 33-66%). Second-line PSA declines > or = 50% were achieved by 61% of patients (95% CI, 42-78%) who achieved a first-line PSA decline > or = 50% with ixabepilone, compared with 33% of patients (95% CI, 13-59%) who did not (P = 0.08). Patients who discontinued first-line ixabepilone treatment for disease progression were less likely to achieve a PSA decline > or = 50% in response to second-line, taxane-based therapy compared with patients who discontinued for toxicity or patient preference (36% vs. 71%; P = 0.01). CONCLUSIONS: Second-line taxane chemotherapy after ixabepilone resulted in a substantial frequency of PSA declines. Although patients with ixabepilone-refractory disease were less likely to respond to second-line taxane chemotherapy, 36% did achieve a PSA response. These findings were consistent with incomplete clinical cross-resistance between the taxanes and the epothilones.     

Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States

BackgroundClinical trials have demonstrated the efficacy of several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC); however, real-world data on their use, survival effect, and safety are limited. Using electronic health record data from the Flatiron Health database, we studied real-world treatment patterns and health outcomes in patients with mCRPC.Patients and MethodsWe conducted a retrospective, non-interventional cohort analysis of electronic health record data of patients with confirmed mCRPC between January 2013 and September 2017. The primary objective was to describe real-world treatment patterns, including treatment type, duration, and sequencing. Secondary objectives included describing patient characteristics and clinical outcomes.ResultsOf 2559 patients with mCRPC, 1980 (77%) received at least 1 line of life-prolonging therapy (abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, or radium-223). Of patients receiving first-line therapy, 49% received second-line therapy, and of these, 43% received third-line therapy. Abiraterone/prednisone and enzalutamide accounted for 65% of first-line therapies and 54% of second-line therapies. Docetaxel was the most common third-line therapy (24%). Back-to-back use of abiraterone/prednisone and enzalutamide was common. Radium-223 monotherapy use was 2% in the first-line setting, 3% in the second-line setting, and 8% in the third-line setting. The median overall survival was longer in patients who received life-prolonging therapies (23.7 months; 95% confidence interval: 22.3-25.1 months) than in those who did not (10.1 months; 95% confidence interval: 9.1-11.5 months).ConclusionThese real-world insights on over 2500 patients with mCRPC supplement findings from randomized controlled trials and may help to inform clinical trial design, treatment guidelines, and clinical decision-making.     

Spotlight on Capecitabine in the Management of Advanced Breast Cancer

Capecitabine is an orally administered prodrug of fluorouracil which is indicated in the US and Europe, in combination with docetaxel, for the treatment of patients with metastatic breast cancer failing anthracycline therapy, and as monotherapy for metastatic breast cancer resistant to paclitaxel and anthracycline therapy (US) or failing intensive chemotherapy (Europe). Capecitabine is also approved for use in metastatic colorectal cancer. Capecitabine is metabolically activated preferentially at the tumor site, and shows antineoplastic activity and synergy with other cytotoxic agents including cyclophosphamide or docetaxel in animal models. Bioavailability after oral administration is close to 100%. In patients with pretreated advanced breast cancer, capecitabine is effective as monotherapy and also in combination with other agents. Combination therapy with capecitabine 1250 mg/m² twice daily for 2 weeks of every 3-week cycle plus intravenous docetaxel 75 mg/m² on day one of each cycle was superior to intravenous monotherapy with docetaxel 100 mg/m² on day one of each cycle. Capecitabine plus docetaxel significantly reduced the risks of disease progression and death by 35% (p = 0.0001) and 23% (p < 0.05), respectively, and significantly increased median survival (p < 0.05) and objective response rates (p < 0.01). Efficacy has also been demonstrated with capecitabine monotherapy and combination therapy in previously untreated patients in preliminary trials. The most common adverse effects occurring in patients receiving capecitabine monotherapy include lymphopenia, anemia, diarrhea, hand-and-foot syndrome, nausea, fatigue, hyperbilirubinaemia, dermatitis and vomiting (all >25% incidence). While gastrointestinal events and hand-and-foot syndrome occurred more often with capecitabine than with paclitaxel or a regimen of cyclophosphamide, methotrexate and fluorouracil (CMF), neutropenic fever, arthralgia, pyrexia and myalgia were more common with paclitaxel, and nausea, stomatitis, alopecia and asthenia were more common with CMF. The incidence of adverse effects and hospitalization was similar in patients receiving capecitabine plus docetaxel and those receiving docetaxel monotherapy. In conclusion, capecitabine, an oral prodrug of fluorouracil which is activated preferentially at the tumor site, is an effective and convenient addition to the intravenous polychemotherapeutic treatment of advanced breast cancer in pretreated patients, and also has potential as a component of first-line combination regimens. Combined capecitabine plus docetaxel therapy resulted in similar rates of treatment-related adverse effects and hospitalization to those seen with docetaxel monotherapy. Capecitabine is also effective as monotherapy in pretreated patients and phase II data for capecitabine as first-line monotherapy are also promising. While gastrointestinal effects and hand-and-foot syndrome occur often with capecitabine, the tolerability profile was comparatively favorable for other adverse effects (notably, neutropenia and alopecia).     

Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020

Almost half of the new cases of colorectal cancer concern patients aged ≥70 years. However, very few clinical trials have specifically included older patients. As a consequence, the treatment of these patients is controversial because the balance between clinical benefits and toxicities remains uncertain. In patients without comorbidities and with an ECOG performance score of 0–1, treatment indications are similar to those of younger patients. For frail patients, chemotherapy is possible, but a comprehensive geriatric assessment is recommended.Anti-EGFR (epidermal growth factor receptor) therapy is indicated either in combination with chemotherapy in the first-line or second-line setting or as monotherapy in the third-line setting (i.e., after failure of chemotherapy). For fit older patients, clinical trials that compared chemotherapy alone with doublet chemotherapy plus anti-EGFR in either first-line or second-line setting suggested that age is not an absolute contraindication for the use of this regimen. In frail patients, anti-EGFR monotherapy in the first-line, second-line or third-line setting has shown feasibility and antitumor activity and had mainly cutaneous toxicities that were easily managed. In any case, administration of treatment must be very cautious in older patients and the treatment dose needs to be adapted according to comorbidities.     

Ceftaroline for the treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus: a case series

Despite limited clinical data, ceftaroline is commonly used for treatment of complicated, invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). A retrospective chart review was conducted of adult patients receiving ceftaroline for MRSA osteomyelitis admitted between April 2011 and March 2016 at a five-hospital system. Twelve patients met the inclusion criteria. All patients received prior antimicrobial therapy with a median time to switch to ceftaroline of 45.5 days. Five of the 12 patients (41.7%) met criteria for ceftaroline failure. Patients with vertebral osteomyelitis (58%) had a longer length of stay, longer ceftaroline treatment, but similar success rates to those with non-vertebral osteomyelitis (57% vs. 60%). Ceftaroline is a viable alternative for a challenging patient population that has failed or are unable to receive other therapies.     

The association of clinical outcome to first-line VEGF-targeted therapy with clinical outcome to second-line VEGF-targeted therapy in metastatic renal cell carcinoma patients

There are many active drugs to treat metastatic renal cell carcinoma (mRCC) patients who progress through their first-line vascular endothelial growth factor (VEGF) inhibitor. Many clinicians choose a second-line VEGF inhibitor based on the type of response to first-line VEGF inhibitor, without data supporting this practice. This study was conducted to determine the association of response to second-line VEGF inhibitor with response to first-line VEGF inhibitor. All mRCC patients in participating centers of the International mRCC Database Consortium who were treated from January 2004 through June 2011 with a second-line VEGF inhibitor after failure of a different first-line VEGF inhibitor were retrospectively identified. The primary outcome is objective response rate (ORR) and the secondary outcome is progression-free survival (PFS) in each line of therapy. Of 1,602 total database patients, 464 patients received a first- and second-line VEGF inhibitor. The ORR to first-line therapy was 22 %, and the ORR to second-line therapy was 11 %. The ORR to second-line therapy was not different among patients achieving partial response versus stable disease versus progressive disease to first-line therapy (14 % vs. 10 % vs. 11 %, respectively; chi-squared trend test p?=?0.17). The median PFS on first-line VEGF-targeted therapy was 7.5 months (95 % CI, 6.6–8.1), and the median PFS on second-line VEGF inhibitor was 3.9 months (95 % CI, 3.6–4.5). There was no correlation between first-line and second-line PFS (Pearson correlation coefficient 0.025; p?=?0.59). The clinical response to a second-line VEGF inhibitor is not dependent on response to the first-line VEGF-inhibitor. Further studies are needed to define clinical parameters that predict response to second-line therapy to optimize the sequence of VEGF-targeted therapy in metastatic RCC patients.     

Real-World Pattern of Treatment and Clinical Outcomes of EGFR-Mutant Non-Small Cell Lung Cancer in a Single Academic Centre in Quebec

The discovery of EGFR tyrosine kinase inhibitors (TKI) for the treatment of EGFR mutant (EGFRm) metastatic NSCLC is regarded as a landmark in lung cancer. EGFR-TKIs have now become a standard first-line treatment for EGFRm NSCLC. The aim of this retrospective cohort study is to describe real-world patterns of treatment and treatment outcomes in patients with EGFRm metastatic NSCLC who received EGFR-TKI therapy outside of clinical trials. One hundred and seventy EGFRm metastatic NSCLC patients were diagnosed and initiated on first-line TKI therapy between 2004 and 2018 at the Peter Brojde Lung Cancer Centre in Montreal. Following progression of the disease, 137 (80%) patients discontinued first-line treatment. Moreover, 80/137 (58%) patients received second-line treatment, which included: EGFR-TKIs, platinum-based, or single-agent chemotherapy. At the time of progression on first-line treatment, 73 patients were tested for the T790M mutation. Moreover, 30/73 (41%) patients were found to be positive for the T790M mutation; 62/80 patients progressed to second-line treatment and 20/62 were started on third-line treatment. The median duration of treatment was 11.5 (95% CI; 9.62–13.44) months for first-line treatment, and 4.4 (95% CI: 1.47–7.39) months for second-line treatment. Median OS from the time of diagnosis of metastatic disease was 23.5 months (95% CI: 16.9–30.1) and median OS from the initiation of EGFR-TKI was 20.6 months (95% CI: 13.5–27.6). We identified that ECOG PS ≤ 2, presence of exon 19 deletion mutation, and absence of brain metastases were associated with better OS. A significant OS benefit was observed in patients treated with osimertinib in second-line treatment compared to those who never received osimertinib. Overall, our retrospective observational study suggests that treatment outcomes in EGFRm NSCLC in real-world practice, such as OS and PFS, reflect the result of RCTs. However, given the few observational studies on real-world treatment patterns of EGFR-mutant NSCLC, this study is important for understanding the potential impact of EGFR-TKIs on survival outside of clinical trials. Further real-world studies are needed to characterize patient outcomes for emerging therapies, including first-line osimertinib use and combination of osimertinib with chemotherapy and potential future combination of osimertinib and novel anticancer drug, outside of a clinical trial setting.     

Predictors of response to second-line endocrine therapy for breast cancer

This study reports on factors predicting response tosecond-line endocrine therapy in 250 patients with breastcancer for which they were assessable for responseby the International Union Against Cancer (UICC) criteria.Clinical details relating to first-line endocrine therapy wereavailable for all patients. We have not includedin this study patients who received first-line endocrinetherapy but did not or have not yetproceeded to second-line hormone therapy – e.g. diedfrom rapidly progressive disease, started chemotherapy for rapidlyprogressive disease, or remained in long-term remission onfirst-line endocrine therapy.One hundred and fifty nine patients (72%) achievedremission (objective response and static disease [OR +SD]) on first-line endocrine therapy with a medianduration of 19 months. For second-line endocrine therapythe remission rate was 53% (132/225) with amedian duration of 15 months. Tumour grade andoestrogen receptor status of the primary tumour wereshown to be independent predictors of response tosecond-line endocrine therapy while response to first-line endocrinetherapy was a predictor of the duration ofresponse to second-line endocrine therapy. In the sub-groupof patients who showed OR or SD toboth first and second-line therapies, there was nocorrelation between the time to progression (TTP) onfirst and second-line therapies.     

Second-line therapy for small-cell lung cancer

Small-cell lung cancer (SCLC) recurs in the majority of patients, even though most patients respond to first-line therapy. Therefore second-line therapy is considered in almost all patients with SCLC in the course of disease. Efficacy of second-line chemotherapy is much lower than that of first-line treatment, but it can provide significant palliation and prolongation of survival for many patients. Patients receiving second-line therapy are divided into relapsed and refractory patients. Relapsed disease is defined as relapse or progression at least 3 months after the end of first-line therapy. All other situations, including a treatment-free interval <3 months or no response to first-line therapy, are termed refractory disease. The benefit from second-line chemotherapy is highest in patients with relapsed disease. Topotecan monotherapy improves survival and quality of life, as well as cancer-related symptoms in the second-line setting. Alternatively, doxorubicin-based combination therapy can be administered with a similar outcome but a slightly lower rate of symptom control. In refractory patients no standard therapy exists. Amrubicin, a novel anthracyline, showed promising activity in refractory and relapsed patients. Phase III trials are ongoing. Other agents with activity include irinotecan, paclitaxel, docetaxel, gemcitabine, bendamustine and vinorelbine.     

Bevacizumab-containing chemotherapy for non-small cell lung cancer patients: a population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group

To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC patients were evaluated at 14 sites (17 hospital departments) in a prefecture of Japan between December 2009 and August 2011. Complete data sets were obtained from 159 patients with NSCLC. The median age was 66?years, and 34.0?% of the patients were 70?years or older. The overall response rate to bevacizumab therapy was 41.6?%, and the disease control rate was 78.5?%. In 88 patients who received bevacizumab-containing chemotherapy as first-line therapy, the response and disease control rates were 55.0 and 78.9?%, respectively. The incidence of clinically significant (grade 3 or more) adverse events was generally low: proteinuria occurred in 2 (1.3?%) patients, hypertension in 2 (1.3?%), hemoptysis in 1 (0.6?%), and interstitial pneumonia in 1 (0.6?%). The time to treatment failure (TTF) in the 159 patients was 169?days, and the median overall survival (OS) was 580?days. In patients who received bevacizumab-containing chemotherapy as first-line therapy, the TTF and OS were 152 and 520?days, respectively. The difference in TTF between patients who received bevacizumab-containing chemotherapy as first-line therapy and those who received it as second-line or later-line therapy was not significant (p?=?0.4971). With regard to first-line therapy, the difference in TTF between patients treated with carboplatin?+?pemetrexed?+?bevacizumab and those treated with carboplatin?+?paclitaxel?+?bevacizumab was not significant (p?=?0.9435). We deduced that bevacizumab-containing chemotherapy is effective against NSCLC and also tolerable in clinical practice.     

A Prospective,Open-Label Noncomparative Study with Piperacillin-Tazobactam Monotherapy as Management of Fever in Patients with Acute Leukemia

Abstract

We evaluated the efficacy of piperacillin-tazobactam monotherapy as empiric therapy of fever in acute leukemia patients in a total of 80 consecutive febrile episodes. The overall success rate was 75% with success without modification in 34% (afebrile at 72 h) and an overall death rate of 10%. No significant differences were seen in correlation between clinical outcome and phases of underlying disease. The success without modification was higher in patients with fever of unknown origin (FUO) than in those with documented infections (47% and 25% respectively). There were no significant differences in correlations between clinical response and degree of neutropenia. Our study suggests that empirical first-line monotherapy with piperacillin-tazobactam may be a reasonable option in patients with acute leukaemia, although in documented infections the response is frequently inadequate.     

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective

The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.

Patients and methods

One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy.

Results

The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001).

Conclusions

Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.     

Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients

The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy. Two different schedules of ifosfamide were investigated in a randomised manner: Ifosfamide was given either at a dose of 5 g/m² over 24 h (5 g/m²/1 day), every 3 weeks or at a dose of 3 g/m² per day, administered over 4 h on three consecutive days (3 g/m²/3 days), every 3 weeks. Both schedules were given as first-line or second-line chemotherapy. A total of 182 patients was entered, 103 in first- and 79 in second-line, of whom 8 patients were ineligible, 5 in the first- and 3 in the second-line study. Most patients had a leiomyosarcoma, 46 of the 98 in the first-line and 34 of the 76 in the second-line. The two study arms were well balanced in both the first- and second-lines with respect to sex, age and performance status. In first-line treatment, 5 g/m²/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m²/3 days. As second-line treatment, the 24-h infusion yielded: one CR and one PR (RR 6%) and the 3-day schedule one CR and two PR (RR 8%). Survival did not differ between the two regimens. The major World Health Organization (WHO) grade 3 and 4 toxicities encountered were: leucopenia in 19% of all courses in the first-line and 32% in the second-line with the 5 g/m²/1 day, while for the 3 g/m²/3 days schedule the rates were 57 and 63% respectively. Grade 3 or 4 infections were seen in 4% of patients treated with 5 g/m²/1 day first-line and 10% of patients given 3 g/m²/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m²/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m², given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m² over 24 hours schedule resulted in a disappointing response rate.     

Clinical Outcomes of First-line Sunitinib Followed by Immuno-oncology Checkpoint Inhibitors in Patients With Metastatic Renal Cell Carcinoma

BackgroundThe present retrospective, longitudinal cohort study assessed the association between the first-line sunitinib treatment duration and clinical outcomes with second-line immuno-oncology (IO) therapy among patients with metastatic renal cell carcinoma (mRCC).Patients and MethodsA total of 161 patients with mRCC who had been treated with first-line sunitinib and subsequent IO therapy from select International mRCC Database Consortium centers were included. The overall survival, time to next therapy, time to treatment discontinuation, and real-world physician-assessed best response measured from IO therapy initiation were analyzed and compared between patients treated with first-line sunitinib for ≥ 6 months and those treated for < 6 months.ResultsThe 116 patients treated with sunitinib for ≥ 6 months tended to be older and to have a better International mRCC Database Consortium risk than the 45 patients treated for < 6 months (favorable, 36% vs. 8%, P = .001; intermediate, 59% vs. 70%, P = .21; poor, 5% vs. 22%, P = .007). The receipt of sunitinib for ≥ 6 months versus < 6 months was associated with longer survival (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = .02). No significant association was observed between the first-line sunitinib duration and second-line IO outcomes, including the time to next therapy (HR, 0.89; 95% CI, 0.52-1.51; P = .66), time to treatment discontinuation (HR, 0.85; 95% CI, 0.54-1.34; P = .49), and tumor response (odds ratio, 0.73; 95% CI, 0.22-2.49; P = .62).ConclusionsWe found no statistically significant association between the first-line sunitinib duration and clinical outcomes with second-line IO therapy. Patients receiving first-line sunitinib for ≥ 6 months compared with < 6 months was associated with better overall survival, although potential unadjusted confounders could have been present. These findings support the paradigm that previous therapy will not dictate the effectiveness of subsequent immunotherapy.     

Comparative efficacy of vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor as second-line therapy in patients with metastatic renal cell carcinoma after the failure of first-line VEGF TKI

Sequential therapy is a standard strategy used to overcome the limitations of targeted agents in metastatic renal cell carcinoma. It remains unclear whether a mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line therapy after first-line vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) has failed than the alternative, VEGF TKI. A clinical database was used to identify all patients with renal cell carcinoma who failed at first-line VEGF TKI and then treated with second-line VEGF TKI or mTOR inhibitors in the Asan Medical Center. Patient medical characteristics, radiological response and survival status were assessed. Of the 83 patients who met the inclusion criteria, 41 received second-line VEGF TKI [sunitinib (n?=?16) and sorafenib (n?=?25)] and 42 were treated with mTOR inhibitors [temsirolimus (n?=?11) and everolimus (n?=?31)]. After a median follow-up duration of 23.9?months (95?% CI, 17.8?C30.0), progression-free survival was 3.0?months for both groups [hazard ratio (HR, VEGF TKI vs. mTOR inhibitor)?=?0.97, 95?% CI 0.59?C1.62, P?=?0.92]. Overall survival was 10.6?months for the VEGF TKI group and 8.2?months for the mTOR inhibitor group (HR?=?0.98, 95?% CI 0.57?C1.68, P?=?0.94). The two groups did not differ significantly in terms of disease control rate (51?% for VEGF TKI and 59?% for mTOR inhibitor, P?=?0.75). Second-line VEGF TKI seems to be as effective as mTOR inhibitors and may be a viable option as a second-line agent after first-line anti-VEGF agents have failed.     

Randomized phase II study of weekly paclitaxel versus paclitaxel and carboplatin as second-line therapy in disseminated melanoma: a multicentre trial of the Dermatologic Co-operative Oncology Group (DeCOG)

Stage melanoma IV has a poor prognosis, with a median survival time between 3 and 11 months from the diagnosis of distant metastases. Response rates in first-line regimens are around 20%. To date, no second-line treatment has been established. We performed a randomized, multicentre, second-line clinical phase II study of paclitaxel either as monotherapy or combined with carboplatin given on an outpatient basis. In arm A, paclitaxel was administered at a dose of 100 mg/m2 intravenously on day 1 each week for 6 weeks. In arm B, paclitaxel was administered at a dose of 80 mg/m2 intravenously followed by carboplatin 200 mg/m2 on day 1 each week for 6 weeks. The next cycle was administered after a 2 week intermission. The response rate, survival time, time-to-progression and toxicity were assessed in both arms. The study was stopped after 40 patients because the overall response rate was below 10% in both arms. The median survival time after initiation of second-line treatment was 209 days (+/- 196 days) for patients treated with paclitaxel only, and 218 days for those treated with paclitaxel/carboplatin. The median time-to-progression was around 56 days in both arms. Two partial responses were observed after 16 weeks, lasting for 8 and 12 weeks, respectively. Although both treatment modalities were well tolerated, haematological toxicity was higher in the combination arm. This is so far the largest second-line clinical phase II study reported in melanoma. However, paclitaxel with or without carboplatin had only limited efficacy, and the combination of these drugs adds significantly to haematological toxicity without improving response or survival rates.     

雷替曲塞或氟尿嘧啶联合伊立替康二线治疗晚期结直肠癌疗效分析

目的 观察雷替曲塞或氟尿嘧啶联合伊立替康二线治疗晚期结直肠癌的近期疗效和不良反应。方法 对蚌埠医学院第一附属医院收治的52例经一线FOLFOX方案治疗失败的晚期结直肠癌患者进行二线治疗。A组（25例）化疗方案为雷替曲塞联合伊立替康,B组（27例）化疗方案为氟尿嘧啶联合伊立替康及亚叶酸钙,比较两组二线治疗的临床疗效、不良反应及生存情况。结果 A组和B组有效率分别为36%和11.5%,差异有统计学意义（P﹤0.05）,疾病控制率分别为76.0%和57.7%,差异无统计学意义（P>0.05）,中位疾病进展时间分别为6.0月和4.5月,差异无统计学意义（P>0.05）。结论 雷替曲塞联合伊立替康方案二线治疗晚期结直肠癌疗效肯定,不良反应能耐受,使用方便,值得临床上推荐使用。