Prognosis and Treatment Outcomes of Bone Metastasis in Gallbladder Adenocarcinoma: A SEER-Based Study.

BACKGROUND: Gallbladder carcinoma (GBC) is a rare, aggressive malignancy comprising 0.5% of gastrointestinal cancers. It has poor survival outcomes due to its insidious onset, lack of standardized screening, and limited therapies. Advanced-stage diagnosis with liver, lymph node, and peritoneal metastasis is common, while bone metastasis is rare. The knowledge on bone metastasis in GBC is limited to case reports and small series, and its clinical significance is largely unexplored. METHODS: The study extracted the demographic and clinical variables of patients with metastatic (M1) gallbladder adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2020. Descriptive statistics were used to analyze the demographic characteristics. The multivariate Cox regression analysis was used to calculate the hazard ratio. The overall survival (OS) was assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare the survival between the groups. RESULTS: A total of 2724 patients were included in the study. A total of 69% of the patients were female, and the median age was 68 (range 24-90+). A total of 7.4% of the patients had bone metastasis on diagnosis. The multivariate Cox analysis identified bone metastasis as an independent mortality risk factor in metastatic GBC (HR 1.50, p < 0.001). The patients were divided into two age groups: a younger age group (18-74 years) and an older age group (75+ years). In the younger group, the median OS with and without bone metastasis was 3 and 5 months, respectively (p < 0.0001). In the older age group, there was no significant difference in the OS between the patients with and without bone metastasis (p = 0.35). In the younger group who were treated with chemotherapy, the patients with bone metastasis had a significantly worse OS (median OS 5 months vs. 8 months, p < 0.0001). In the untreated group, the patients with bone metastasis in the younger age group had a significantly worse OS (median OS 1 month vs. 2 months, p = 0.014). In the patients with bone metastasis, those who did not receive chemotherapy had a significantly worse OS than those who were treated with chemotherapy in both age groups (younger age group: median OS 1 month vs. 5 months, p < 0.0001 and older age group: median OS 1 month vs. 5 months, p = 0.041). CONCLUSIONS: Our findings suggest that the presence of bone metastasis in gallbladder adenocarcinoma is an independent prognostic factor associated with unfavorable survival outcomes in the younger age group (18-74 years). However, in the older age group (75+ years), the presence of bone metastasis did not impact the survival. Treatment with chemotherapy was associated with extended survival in all patients. Thus, early detection and aggressive management of bone metastasis, including the consideration of chemotherapy, may be crucial in improving the OS and quality of life for individuals with gallbladder adenocarcinoma.

A phase II study of neoadjuvant liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in pancreatic adenocarcinoma.

For patients with localized pancreatic cancer with minimal vascular involvement, optimal survivability requires a multidisciplinary approach of surgical resection and systemic chemotherapy. FOLFIRINOX is a combination chemotherapy regimen that offers promising results in the perioperative and metastatic settings; however, it can cause significant adverse effects. Such toxicity can negatively impact some patients, resulting in chemotherapy discontinuation or surgical unsuitability. In an effort to reduce toxicities and optimize outcomes, this investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug delivery and potentially reduce toxicity. This regimen, NALIRIFOX, has the potential to be both safer and more effective when administered in the preoperative setting.

For patients with pancreatic cancer with little to no cancer near the blood vessels, the best life expectancy usually requires surgery and chemotherapy. FOLFIRINOX is a chemotherapy medicine that offers promising results for both patients getting surgery and for patients with widespread disease. However, it can cause harmful side effects. The side effects can be so bad that the chemotherapy has to be stopped or that surgery is no longer possible. In order to reduce the harmful side effects and improve outcomes, this investigation looks into the safety and practicality of using a different version of one of the medicines. The different version hopes to improve drug delivery and reduce harmful side effects. This regimen, NALIRIFOX, can be safer and more effective in patients awaiting surgery. Clinical Trial Registration: UF-STO-PANC-004 (NCT03483038) (ClinicalTrials.gov).

Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis.

Background: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.

Updates in the use of targeted therapies for the treatment of cholangiocarcinoma.

OBJECTIVE: Many patients with cholangiocarcinoma (CCA) are not surgical candidates, and the survival benefit of chemotherapy is less than 12 months. Several mutations and mutational clusters have recently been identified in CCA, some of which are pharmacologically targetable. The emergence of targeted therapies has significantly altered the treatment landscape of CCA and improved the prognosis for advanced or metastatic CCA. The purpose of this review is to describe past and current treatment strategies of CCA with a focus on FDA-approved targeted therapies. DATA SOURCES: A systematic evaluation of all FDA-approved targeted treatments for CCA through October 2022 was conducted. Information related to pharmacology, clinical efficacy, and safety was gathered from the package insert, and clinical trial data. DATA SUMMARY: As of the writing of this review, four targeted agents are FDA approved for the treatment of locally advanced or metastatic CCA. These agents include the IDH1 inhibitor ivosidenib and the FGFR2 inhibitors pemigatinib, infigratinib, and futibatinib. Collectively, these agents have provided additional treatment options for select patients with previously treated locally advanced or unresectable CCA. These agents have also contributed to the development of other targeted therapies for the treatment of CCA and have opened the door for the exploration of novel treatment combinations such as chemotherapy and immunotherapy, which have recently become a front-line treatment option. CONCLUSIONS: Four targeted small molecule agents have emerged as effective therapies in the second-line setting for CCA, which has immensely changed the treatment landscape and directly led to further investigation of targeted agents and immunotherapy as treatment for CCA.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study.

BACKGROUND: Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. MATERIALS AND METHODS: A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. RESULTS: There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). CONCLUSIONS: In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.

PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials.

Radiopharmaceuticals have been utilized for men with advanced prostate cancer for decades. Older agents, seldom used today, provided palliation for bone metastatic pain. In 2013, the alpha emitter radium-223 provided a catalyst for the field by prolonging survival in men with metastatic castrate-resistant prostate cancer (mCRPC). Recently radioisotopic therapies have gained further interest with the development and FDA approval of 177 lutetium (177Lu)-PSMA-617 (also known as lutetium Lu-177 vipivotide tetraxetan). This agent targets the prostate-specific membrane antigen (PSMA) expressed on the cell surface of prostate cancer cells with a beta-emitting isotope (177Lu). This clinical review summarizes key data reported from 177Lu-PSMA-617 clinical trials, including data from the phase III VISION trial which were pivotal for regulatory approval in heavily pretreated PSMA-PET-positive patients with mCRPC. The current field of radiopharmaceuticals is in a rapid state of flux. Additional phase III trials are now ongoing in patients with mCRPC and in patients with metastatic castrate-sensitive prostate cancer. The results from these potential practice-changing trials are highly anticipated. Earlier phase trials (I/II) are in progress examining combination therapies, radiolabeled monoclonal antibodies, and novel compounds. Studies of PSMA-targeted therapies using both beta emitters such as 177Lu and novel alpha emitters such 225 actinium are in progress. During the next decade, radiopharmaceuticals will likely play a central role in the management of patients with advanced prostate cancer.

Pneumocystis jirovecii pneumonia in a patient treated with trastuzumab-deruxtecan.

Trastuzumab-deruxtecan (T-DXd) is a novel antibody drug conjugate that has improved treatment outcomes in patients with ERBB2-positive cancer, including locally advanced or metastatic gastric and gastro-oesophageal junction adenocarcinoma. One of the reported side effects of this medication is drug-induced pneumonitis. We present in this case report, a diagnostic dilemma of a patient presenting with clinical and radiographical features of drug-induced pneumonitis but was found to have pneumocystis jirovecii pneumonia (PJP). Our case is the first of PJP in a patient treated with T-DXd, highlighting the increasing incidence of this opportunistic infection in patients with solid malignancy. It also highlights the clinical and radiographical similarities between the PJP and drug-induced pneumonitis.

Advanced Hepatocellular Carcinoma in Adults Without Cirrhosis: A Single-Institution Retrospective Review.

Background: Although up to one in five cases of hepatocellular carcinoma (HCC) occurs in patients without cirrhosis, there is scarce literature characterizing non-cirrhotic HCC (NCHCC). Existing NCHCC research is primarily limited to surgical case series and there is a lack of data on unresectable NCHCC. Aim: The purpose of this retrospective review was to compare the characteristics of unresectable NCHCC and cirrhotic hepatocellular carcinoma (CHCC). Methods: A retrospective chart review of adult patients with unresectable HCC treated from 2007 to 2017 was performed at the University of Florida Shands Hospital. The data set was stratified into two cohorts: NCHCC and CHCC. Continuous variables were compared using Wilcoxon-Mann-Whitney tests and Kruskal-Wallis rank-sum tests. Categorical variables were compared using Pearson's Chi-squared tests and Fisher's exact tests. Overall survival was explored utilizing the Kaplan-Meier and log-rank method. Results: There were 1494 adult patients included in the final analysis, including 264 patients (17.7%) with NCHCC and 1230 patients (82.3%) with CHCC. Median age was 61.0 years old and median follow-up time was 30.2 months. NCHCC patients were older than CHCC patients (66.3 years vs 61.9 years; p < 0.0001). NHCC tumors were larger than CHCC tumors (7.92 ± 4.85 vs 4.38 ± 3.12 cm; p < 0.0001) and more likely to be associated with distant metastases (23.35% vs 15.91%; p = 0.0055). There was no difference in overall survival, with a median of 23.5 months in NCHCC and 22.4 months in CHCC (p = 0.9196). Conclusion: Our findings suggest that unresectable NCHCC and CHCC have unique characteristics but similar overall survival. To the best of our knowledge, this is the largest comparison of CHCC and NCHCC.

Atezolizumab plus tivozanib for immunologically cold tumor types: the IMMCO-1 trial.

Immune checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not clinically effective in immunogenically 'cold' tumors such as pancreatic cancer, prostate cancer and neuroendocrine tumors. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade in tumors that have traditionally shown a lack of clinical response to immunotherapy. This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

Tivozanib for the treatment of advanced renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) accounts for 2.4% of cancers, with clear cell kidney cancer being the most common histologic subtype. Despite recent therapeutic advances, the prognosis for patients with advanced disease remains poor, with a 5-year survival rate of only 13.9% reported in the United States. Tivozanib is a novel inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1, -2, and -3 and has recently been approved by the US FDA for use in patients with relapsed or recurrent advanced RCC following two or more prior systemic therapies. AREAS COVERED: Here, the authors provide a review focusing on the development of tivozanib, compare tivozanib to other agents in the VEGFR inhibitor class, detail how tivozanib fits into current treatment landscape, and describe ongoing studies involving this agent. EXPERT OPINION: Given tivozanib's excellent safety profile and demonstrated clinical benefit in patients with pretreated disease, tivozanib is likely to be heavily utilized in the later-line setting. The ongoing TINIVO-2 study may further impact the treatment landscape by evaluating the use of tivozanib plus nivolumab in patients who have progressed on an immune checkpoint inhibitor.

Clinical Updates for Colon Cancer Care in 2022.

Colon cancer needs better screening and treatment options. Its incidence in the young population is rising. Recent changes in guidelines recommend beginning screening for colon cancer at the age of 45. Circulating tumor DNA presents an opportunity to select patients for administration of adjuvant chemotherapy. Immunotherapy is an option for patients with a deficiency in mismatch repair proteins. However, its efficacy outside of this group of patients remains a challenge. Targeted therapies such as BRAF inhibitors are an option for patients with poor prognosis, for whom cytotoxic chemotherapy is not as effective. This review presents the recently published evidence regarding screening and treating patients with colon cancer.

Administration of Immune Checkpoint Inhibitors Near the End of Life.

PURPOSE: Recent literature suggests an increasing use of systemic treatment in patients with advanced cancer near the end of life (EOL), partially driven by the increasing adoption of immune checkpoint inhibitors (ICIs). While studies have identified this trend, additional variables associated with ICI use at EOL are limited. Our aim was to characterize a population of patients who received a dose of ICI in the last 30 days of life. METHODS: We performed a manual retrospective chart review of patients ≥ 18 years who died within 30 days of receiving a dose of ICI. Metrics such as Eastern Cooperative Oncology Group performance status (ECOG PS), number of ICI doses, need for hospitalization, and numerous other variables were evaluated. RESULTS: Over a 4-year time period, 97 patients received an ICI at EOL. For 40% of patients, the ICI given in the 30 days before death was their only dose. Over 50% of patients had an ECOG PS of ≥ 2, including 17% of patients with an ECOG PS of 3. Over 60% were hospitalized, 65% visited the emergency department, 20% required intensive care unit admission, and 25% died in the hospital. CONCLUSION: Our study contributes to the ongoing literature regarding the risks and benefits of ICI use in patients with advanced cancer near the EOL. While accurate predictions regarding the EOL are challenging, oncologists may routinely use clinical factors such as ECOG PS along with patient preferences to guide recommendations and shared decision making. Ultimately, further follow-up studies to better characterize and prognosticate this population of patients are needed.

Predicting Complete Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

Muscle-invasive bladder cancer is a life-threatening disease best managed with multimodal therapy. Neoadjuvant chemotherapy prior to cystectomy significantly improves survival with the greatest benefit noted in patients with a complete pathologic response noted at cystectomy. While radical cystectomy is currently an important part of the treatment plan, surgical morbidity remains high. Accurate prediction of complete responses to chemotherapy would enable avoiding the morbidity of radical cystectomy. Multiple clinical, pathologic, molecular, and radiographic predictors have been evaluated. Clinical and standard pathologic findings have not been found to be accurate predictors of complete response. To date, tumor genomic findings have been the most promising and have led to multiple clinical trials to evaluate if bladder preservation is possible in select patients. Radiomics has shown initial promise with larger validation series needed. These predictors can be further characterized as treatment specific and non-treatment specific. With the potential changing landscape of neoadjuvant therapy prior to radical cystectomy and the limitations of individual predictors of a complete response, a panel of several biomarkers may enhance patient selection for bladder preservation. The aim of this review is to summarize predictors of complete response to neoadjuvant chemotherapy.

Trends in Use of Granulocyte Colony-Stimulating Factor Following Introduction of Biosimilars Among Adults With Cancer and Commercial or Medicare Insurance From 2014 to 2019.

Importance: The introduction of biosimilars and novel delivery devices between 2014 and 2019 may have changed the utilization of granulocyte colony-stimulating factors (G-CSF). Objective: To assess utilization trends of G-CSFs for primary prophylaxis of febrile neutropenia (FN) among patients with cancer receiving myelosuppressive chemotherapy with commercial or Medicare insurance. Design, Setting, and Participants: This cross-sectional study assessed G-CSF utilization trends overall and stratified by regimen febrile neutropenia risk level. Associations between patient characteristics and G-CSF use were evaluated. Patients with cancer, including breast, lung, colorectal, esophageal and gastric, pancreatic, prostate, ovarian, and non-Hodgkin lymphomas, initiating myelosuppressive chemotherapy courses were included from the 2014 to 2019 commercial insurance and 2014 to 2018 Medicare fee-for-service claims databases. Data were analyzed from March to June 2021. Exposures: Year of chemotherapy initiation. Main Outcomes and Measures: The main outcomes were use and trends of G-CSFs for primary prophylaxis, from completion to 3 days after in the first chemotherapy cycle. Results: In total, 86 731 chemotherapy courses (mean [SD] age, 57.7 [11.5] years; 57 838 [66.7%] women and 28 893 [33.3%] men) were identified from 82 410 patients in the commercial insurance database and 32 398 chemotherapy courses (mean [SD] age, 71.8 [8.3] years; 18 468 [57.0%] women and 13 930 [43.0%] men) were identified from 30 279 patients in the Medicare database. Among the commercially insured population, 39 639 patients (45.7%) received G-CSFs, and 12 562 patients (38.8%) received G-CSFs among Medicare insured patients. Overall G-CSF use increased significantly throughout the study period in both populations, from 45.1% (95% CI, 44.4%-45.7%) of patients in 2014 to 47.5% (95% CI, 46.5%-48.5%) of patients in 2019 (P = .001) in the commercially insured population and from 36.0% (95% CI, 34.2%-38.0%) of patients in 2014 to 39.1% (95% CI, 38.1%-40.1%) of patients in 2018 (P < .001) in the Medicare population. The greatest increases in G-CSF use were observed among patients with high FN risk, from 75.0% (95% CI, 74.1%-76.0%) of patients to 83.2% (95% CI, 82.0%-84.2%) of patients (P < .001) among the commercially insured population and 75.3% (95% CI, 71.8%-78.6%) of patients to 86.2% (95% CI, 84.7%-87.6%) of patients (P < .001) among the Medicare population. Use of G-CSFs decreased in the commercially insured population among patients with intermediate FN risk (from 27.5% [95% CI, 26.4%-28.5%] of patients to 20.4% [95% CI, 19.1%-21.7%] of patients; P < .001) or low FN risk (from 19.3% [95% CI, 18.3%-20.4%] of patients to 16.3% [95% CI, 14.7%-18.0%] of patients; P < .001) and remained stable in the Medicare population (intermediate risk: from 26.4% [95% CI, 23.8%-29.2%] of patients to 28.4% [95% CI, 27.0%-29.8%] of patients; P = .35; low risk: from 19.6% [95% CI, 17.0%-22.4%] of patients to 20.9% [95% CI, 19.6%-22.3%] of patients; P = .58). Factors associated with increased odds of G-CSF use included older age (commercial insurance: adjusted odds ratio [aOR], 1.50 [95% CI, 1.41-1.59]; Medicare: aOR, 1.36 [95% CI, 1.08-1.71]), receiving a regimen with high FN risk (commercial insurance: aOR, 16.01 [95% CI, 15.17-16.90]; Medicare: aOR, 17.17 [95% CI, 15.76-18.71]), and history of neutropenia (commercial insurance: 3.90 (3.67-4.15); Medicare: 3.82 (3.50-4.18). Conclusions and Relevance: This cross-sectional study found that utilization of G-CSFs increased among patients with cancer with high FN risk in both a commercially and Medicare-insured population, but 14% to 17% of patients still did not receive preventive treatment.

Primary neuroendocrine tumours of the heart: case report and literature review.

Neuroendocrine tumours occur most frequently in the gastrointestinal tract, lungs, and pancreas. Primary malignant cardiac tumours are uncommon and are usually sarcomas, lymphomas, or, infrequently, mesotheliomas. Primary cardiac neuroendocrine carcinomas are exceedingly rare; only nine have been reported in the literature to date. We report the tenth case of this disorder in a 44-year-old man with a well-differentiated low-grade primary cardiac neuroendocrine carcinoma treated with surgery who remains in remission more than a year later. Our case and review of the literature demonstrate that surgical treatment for well-differentiated primary cardiac neuroendocrine carcinomas can be effective.

Immunotherapy Management in Special Cancer Patient Populations.

Patients with autoimmune disorders, multiple comorbidities, poor performance status, advanced age, and infection with SARS-CoV-2 (COVID-19) each represent unique subgroups of patients with cancer to whom little is known of the effects, benefits, and complications of checkpoint inhibitor (CPI) therapy. Although prospective trials are lacking in these populations, retrospective data and cohort series suggest that these patients can safely receive and benefit from CPI therapy. Here, we review the relevant data available and offer clinical recommendations in managing these complex patients with CPI therapy, where otherwise indicated.

Activity of Sorafenib Plus Capecitabine in Previously Treated Metastatic Colorectal Cancer.

LESSONS LEARNED: Treatment for patients with metastatic colorectal cancer (mCRC) typically involves multiple lines of therapy with eventual development of treatment resistance. In this single-arm, phase II study involving heavily pretreated patients, the combination of sorafenib and capecitabine yielded a clinically meaningful progression-free survival of 6.2 months with an acceptable toxicity profile. This oral doublet therapy is worthy of continued investigation for clinical use in patients with mCRC. BACKGROUND: Capecitabine (Cape) is an oral prodrug of the antimetabolite 5-fluorouracil. Sorafenib (Sor) inhibits multiple signaling pathways involved in angiogenesis and tumor proliferation. SorCape has been previously studied in metastatic breast cancer. METHODS: This single-arm, phase II study was designed to evaluate the activity of SorCape in refractory metastatic colorectal cancer (mCRC). Patients received Sor (200 mg p.o. b.i.d. max daily) and Cape (1,000 mg/m2 p.o. b.i.d. on days 1-14) on a 21-day treatment cycle. Primary endpoint was progression-free survival (PFS) with preplanned comparison with historical controls. RESULTS: Forty-two patients were treated for a median number of 3.5 cycles (range 1-39). Median PFS was 6.2 (95% confidence interval [CI], 4.3-7.9) months, and overall survival (OS) was 8.8 (95% CI, 4.3-12.2) months. One patient (2.4%) had partial response (PR), and 22 patients (52.4%) had stable disease (SD) for a clinical benefit rate of 54.8% (95% CI, 38.7%-70.2%). Hand-foot syndrome was the most common adverse event seen in 36 patients (85.7%) and was grade ≥ 3 in 16 patients (38.1%). One patient (2.4%) had a grade 4 sepsis, and one patient (2.4%) died while on treatment. CONCLUSION: SorCape in this heavily pretreated population yielded a reasonable PFS with manageable but notable toxicity. The combination should be investigated further.