Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801)

Objectives

The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer.

Methods

Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival.

Results

The median age was 60 years (range 37–75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6–16.3) and median overall survival was 28.4 months (95 % CI 22.6–39.1). The overall response rate was 60.0 % (95 % CI 45.2–73.6). Regarding toxicity, the commonest grade 3–4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3–4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3–4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %).

Conclusions

An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

     

A phase II study of carboplatin,pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type <Emphasis Type="Italic">EGFR</Emphasis> (HOT1101)

Background

This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR.

Methods

Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4–6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL).

Results

Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1–6) and 4 (range 1–20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0–72.6%]. The ORR was 48.0% (95% CI 34.8–61.5%), and disease control rate was 86.0% (95% CI 73.8–93.0%). The median PFS and OS were 6.5 months (95% CI 5.8–7.2 months) and 21.4 months (95% CI 15.9–26.9 months), respectively. Although grades ≥?3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment.

Conclusions

Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR.

Trial registration

UMIN000005872.

     

A prospective phase II study of 2-methoxyestradiol administered in combination with bevacizumab in patients with metastatic carcinoid tumors

Purpose

Angiogenesis inhibition has emerged as a potentially promising treatment strategy for neuroendocrine tumors. 2-Methoxyestradiol (2ME2; Panzem^®) is a natural derivative of estradiol with demonstrated anti-angiogenic activity in animal models. We performed a prospective, phase II study of 2ME2, administered in combination with bevacizumab, in patients with advanced carcinoid tumors.

Methods

Thirty-one patients with advanced carcinoid tumors were treated with 2ME2, administered orally at a dose of 1,000 mg four times daily. Patients also received bevacizumab 5 mg/kg intravenously every 2 weeks. Patients were observed for evidence of toxicity, tumor response, and survival.

Results

The combination of 2ME2 and bevacizumab was relatively easily tolerated and was associated with anticipated toxicities for these two agents. No confirmed radiologic responses (by RECIST) were observed. However, 68% of the radiologically evaluable patients experienced at least some degree of tumor reduction, and the median progression-free survival (PFS) time was 11.3 months.

Conclusion

2ME2 and bevacizumab can be safely administered to patients with advanced carcinoid tumors. While major tumor regression was not observed with this regimen, the encouraging median progression-free survival time suggests that this regimen has some degree of antitumor activity and supports the further investigation of angiogenesis inhibitors in this disease.

     

Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients

Purpose

Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors.

Method

The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than ?2 was considered short statured.

Result

Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 ± 14.8 vs 128.7 ± 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09).

Conclusion

Short stature affects a significant number of retinoblastoma survivors.

     

Comparative Safety of Targeted Therapies for Metastatic Colorectal Cancer between Elderly and Younger Patients: a Study Using the International Pharmacovigilance Database

Background

Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly.

Objective

This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life.

Patients and Methods

An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups.

Results

There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56–71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only.

Conclusions

ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies.

     

Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: North Central Cancer Treatment Group Trial N0745 (Alliance)

Background

Angiogenesis has been a major target of novel drug development in hepatocellular carcinoma (HCC). It is hypothesized that the combination of two antiangiogenic agents, sorafenib and bevacizumab, will provide greater blockade of angiogenesis.

Objective

To determine the optimal dose, safety, and effectiveness of dual anti-angiogenic therapy with sorafenib and bevacizumab in patients with advanced HCC.

Patients and Methods

Patients with locally advanced or metastatic HCC not amenable for surgery or liver transplant were eligible. The phase I starting dose level was bevacizumab 1.25 mg/kg day 1 and 15 plus sorafenib 400 mg twice daily (BID) days 1-28. In the phase II portion, patients were randomized to receive bevacizumab and sorafenib at the maximum tolerated dose (MTD) or sorafenib 400 mg BID.

Results

Seventen patients were enrolled in the phase I component. Dose-limiting toxicities included grade 3 hand/foot skin reaction, fatigue, hypertension, alanine/aspartate aminotransferase increase, dehydration, hypophosphatemia, creatinine increase, hypoglycemia, nausea/vomiting, and grade 4 hyponatremia. Seven patients were enrolled in the phase II component at the MTD: sorafenib 200 mg BID days 1-28 and bevacizumab 2.5 mg/kg every other week; 57% (4/7) had grade 3 AEs at least possibly related to treatment. No responses were observed in the phase II portion. Estimated median time to progression and survival were 8.6 months (95% CI: 0.4-16.3) and 13.3 months (95% CI 4.4 – not estimable), respectively.

Conclusions

The MTD of the combination is sorafenib 200 mg twice daily on days 1-28 plus bevacizumab 2.5 mg/kg on days 1 and 15 of a 28-day cycle. In the phase II portion of the trial, concerns regarding excessive toxicity, low efficacy, and slow enrollment led to discontinuation of the trial. (Clinical Trials ID: NCT00867321.)

     

Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study

Purpose

Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent.

Methods

In the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS.

Results

Maximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4–7.8) months, and median OS was 20.6 (11.5–23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3–4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively.

Conclusions

Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.

     

Treatment outcomes of hypofractionated radiotherapy combined with temozolomide followed by bevacizumab salvage therapy in glioblastoma patients aged &gt; 75 years

Background

The optimal treatment for elderly patients with glioblastoma has not been established.

Methods

We retrospectively analyzed the safety and efficacy of hypofractionated radiotherapy (45 Gy/15 fr) combined with temozolomide (TMZ) followed by bevacizumab (BEV) salvage treatment in 18 glioblastoma patients aged?>?75 years.

Results

All of the patients received safe hypofractionated radiotherapy and concomitant TMZ (75 mg/m²), and 14 of 18 patients received maintenance TMZ. We administered BEV to 17 of 18 patients because their Karnofsky Performance Status scores declined and/or recurrence was detected. During the follow-up period (median duration: 17.5 months, range 3–33 months), 12 patients died of their disease. While the median progression-free survival period was 2.5 months, the median overall survival period was 20 months. Adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events grade 3 or 4) occurred in 5 patients.

Conclusion

Hypofractionated radiotherapy combined with TMZ and BEV salvage treatment was found to be safe and effective in glioblastoma patients aged?>?75 years.

     

Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study

Background

In hormone receptor-positive advanced breast cancer, a progression-free survival benefit was reported with addition of bevacizumab to first-line letrozole. However, increased toxicity was observed. We hypothesized that functional age measures could be used to identify patients at risk for toxicity while receiving letrozole plus bevacizumab for hormone receptor-positive advanced breast cancer.

Methods

CALGB 40503 was a phase III trial that enrolled patients with hormone receptor-positive advanced breast cancer randomized to letrozole with or without bevacizumab. Patients randomized to bevacizumab were approached to complete a validated assessment tool evaluating physical function, comorbidity, cognition, psychological state, social support, and nutritional status. The relationship between pretreatment assessment measures and the incidence of grade?≥?3 (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0) adverse events was determined.

Results

One hundred thirteen (58%) of 195 patients treated with letrozole plus bevacizumab completed the pretreatment assessment questionnaire. One patient was excluded due to missing adverse event data. The median age of patients was 56. Frequently reported grade?≥?3 adverse events were hypertension (26%), pain (20%), and proteinuria (7%). Two hemorrhagic events (one grade 5) and 1 thrombosis event occurred. Age?≥?65 years (p?<?0.01), decreased vision (p?=?0.04), and poorer pretreatment physical function measures (p?<?0.05) were found on univariate analysis to be significantly associated with increased incidence of grade?≥?3 adverse events. Upon multivariate analysis, age?≥?65 years (p?=?0.01) and decreased vision (p?=?0.04) remained significant. Univariable and multivariable logistic regression models demonstrated associations between age, vision, the ability to walk up flights of stairs, and grade?≥?3 adverse events.

Conclusions

Age (≥?65 years), decreased vision, and impairments in physical function correlated with increased incidence of toxicity in patients receiving first-line letrozole plus bevacizumab. When evaluating therapy likely to increase toxicity, functional assessment measures can identify patients at increased risk for side effects who may benefit from closer monitoring.

     

The efficacy and safety of capecitabine plus bevacizumab combination as first-line treatment in elderly metastatic colorectal cancer patients

Aim

The optimal treatment in older persons with metastatic colorectal cancer (mCRC) is complicated by a lack of general agreement. The aim of this study was to evaluate the activity of bevacizumab plus capecitabine combination in elderly mCRC patients who were not suitable for chemotherapy with irinotecan and oxaliplatin-containing regimens.

Materials and methods

Seventy years and older patients with metastatic colorectal carcinoma were included in this retrospective study. Bevacizumab was administered at a dose of 7.5 mg/kg on day 1 as an intravenous (IV) infusion over 30–90 min every 21 days, and capecitabine was prescribed at 1000 mg/m² twice daily on days 1–14 of the same 21-day schedule.

Results

Eighty-two consecutive patients (47 men, 35 women) were included in the study. The mean age was 75.5 (SD 3.9, range 70–87). Half of the patients were older than 75 years. There were 55 patients (67.1 %) with a good Eastern Cooperative Oncology Group (ECOG) performance status (PS: 0–1) and the remaining 27 patients (32.9 %) had a poor ECOG performance status (PS: 2). With a median follow-up period of 18.5 months, the median progression-free survival (PFS) was 10 months (95 % CI, 7.8–12.1) and the median OS was 25 months (95 % CI, 18.6–31.3). The main toxicities recorded were non-hematological. Thirty-one patients (37 %) experienced grade 3/4 adverse events, the most common being hand–foot syndrome (9.8 %). No fatal toxicity resulting from this regimen was recorded.

Conclusions

Considering the toxicity profile and survival outcomes, the combination regimen of capecitabine and bevacizumab is a potentially feasible treatment option in elderly mCRC patients.

     

Bevacizumab for recurrent,persistent or advanced cervical cancer: reproducibility of GOG 240 study results in “real world” patients

Purpose

Bevacizumab is the only therapeutic target approved for patients with persistent, recurrent or advanced cervical cancer from a phase III study that combined with chemotherapy; it proves a significant increase in overall survival. To retrospectively assess the efficacy and safety of bevacizumab as the first-line treatment in patients from usual clinical practice with recurrent/persistent or advanced cervical cancer.

Patients and methods

Treatment consisted of cisplatin 50 mg/m² or carboplatin AUC 5 plus paclitaxel 175 mg/m² for 6–8 cycles and bevacizumab 15 mg/kg every 3 weeks up to progression or unacceptable toxicity. The endpoints were progression-free survival (PFS), overall survival (OS), response rates (RR) and toxicity.

Results

Twenty-seven patients were included from January 2014 to June 2017, with a median follow-up 10, 1 months. Eleven percent had recurrent/persistent disease and 89% had metastatic disease at diagnosis. The prior exposition to platinum was 70%. The median PFS and OS were 9, 6 and 21, 5 months, respectively. There was an increase of fistula formation (22%). All of them had pelvic and peritoneal disease at the beginning of treatment and previous treatment with chemoradiotherapy; non-incidence differences were found according to the type of platinum agent used. There were two treatment-related deaths, one from intestinal perforation and another from severe sepsis.

Conclusion

Finally, although our study does have certain limitations, we believe that it can provide useful information and encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with advanced cervical cancer may be associated with outcomes comparable with those obtained in GOG240 study.

     

A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101)

Background

This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC).

Methods

This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m² on day 1 plus capecitabine 800 mg/m² b.i.d. on days 1–14) every 3 weeks. The primary endpoint was the objective tumor response rate.

Results

A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1–70.2%). The median progression-free survival was 9.6 months (95% CI 5.1–11.1 months) and the median overall survival was 23.1 months (95% CI 11.3–36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism.

Conclusions

A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

     

High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab

Purpose

To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab.

Methods

Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0–1) vs. group 2 with high expression (2–3).

Results

Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy.

Conclusions

Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.

     

Management and outcome of children with neuroendocrine tumors of the appendix in Spain: Is there room for improvement?

Purpose

Neuroendocrine tumors (NETs) are, after lymphomas, the most frequent gastrointestinal tumors in children, mainly located in the appendix. Best management remains unclear, given the absence of pediatric guidelines. We present the first Spanish series of pediatric patients with NETs.

Patients and methods

Retrospective study of all pediatric patients (<18 years) with NET treated in four oncology reference institutions in Spain between 1994 and 2015.

Results

Seventeen patients were included. All patients presented with acute abdomen. TNM stage was T1a (82%) and T1b (12%). Extension study was heterogenous, with only 4 patients undergoing an OctreoScan. Four patients met criteria for second surgery (affected surgical margins or mesoappendix invasion), but it was only performed in two. Despite the diverse management, none of the patients relapsed during follow-up.

Conclusions

The disparity in diagnostic tests, second surgery criteria and follow-up shown in this study highlights the need for specific pediatric guidelines.

     

Low-Dose Continuous 5-Fluorouracil Combined with Leucovorin, <Emphasis Type="Italic">nab</Emphasis>-Paclitaxel,Oxaliplatin, and Bevacizumab for Patients with Advanced Pancreatic Cancer: A Retrospective Analysis

Background

Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic.

Objective

In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy.

Patients and Methods

Since July of 2008, we have treated 65 patients with 5FU (180 mg/m²/day × 14 days) via an ambulatory pump. Calcium leucovorin (20 mg/m² IV), nab-paclitaxel (60 mg/m²) IV as a 30-min infusion, and oxaliplatin (50 mg/m²) IV as a 60-min infusion were given on days 1, 8, and 15. Bevacizumab (5 mg/kg) IV over 30 min was administered on days 1 and 15. Cycles were repeated every 28–35 days. There were 42 women and 23 men, and the median age was 59 years. Forty-six patients had stage IV disease.

Results

The median survival was 19 months, with 82% of patients surviving 12 months or longer. The overall response rate was 49%. There were 28 patients who had received prior treatment, 15 of whom responded to therapy. Fifty-two patients had elevated CA 19-9 prior to treatment. Of these, 21 patients had 90% or greater reduction in CA 19-9 levels. This cohort had an objective response rate of 71% and a median survival of 27 months. Thirty patients stopped treatment due to disease progression, and an additional 22 stopped because of toxicity. One patient died while on therapy.

Conclusions

This non-gemcitabine-based regimen resulted in higher response rates and better survival than what is commonly observed with therapy given at conventional dosing schedules. Low-dose continuous (metronomic therapy) cytotoxic chemotherapy combined with antiangiogenic therapy is safe and effective.

     

Retrospective study of nivolumab for patients with recurrent high grade gliomas

Introduction

Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS).

Methods

We retrospectively analyzed HGG patients treated with nivolumab in our institution. We included patients with advanced HGG who received nivolumab at their oncologist’s decision. Patients received nivolumab 3 mg/kg every 2 weeks until confirmed progression, intolerable toxicity, death, or physician decision. Radiographic assessments were performed every 8 weeks.

Results

Between April 2015 and October 2017, 50 HGG patients received nivolumab. 43 patients received nivolumab with bevacizumab. 44 patients were bevacizumab refractory and 7 patients received nivolumab monotherapy. All had received prior radiation and chemotherapy. 39 adverse events (AEs) were noted [most commonly fatigue (16%) and constipation (10%)]. 4 (8%) patients experienced grade 3–4 AEs. 36 (72%) patients experienced stable disease (SD) at the 2-month assessment. Median duration of SD was 4.3 months (5.1 months in the bevacizumab naïve, 3.8 months in the bevacizumab refractory). Median PFS was 4.3 months (95% CI 3.5–5.3); median OS was 6.5 months (95% CI 6.0–8.8).

Conclusion

Treatment with nivolumab therapy was associated with a manageable safety profile. In a subset of patients, there was disease stabilization in heavily pre-treated recurrent HGG.

     

Overall Survival and Metastasis Resections in Patients with Metastatic Colorectal Cancer Using Electronic Medical Records

Purpose

Treatment for patients with metastatic colorectal cancer is chemotherapy commonly combined with monoclonal antibodies against vascular endothelial growth factor (bevacizumab) or epidermal growth factor receptor (cetuximab or panitumumab), the efficacy of which has been proven in randomized controlled trials. The objective of the current retrospective study was to analyze the impact of targeted therapy, adverse events, and dose reduction on overall survival (OS) and metastasis resection rates.

Methods

A hospital-based electronic informatics center was used to gather clinical data and outcome information in a “real-life” setting in a single academic hospital. A total of 178 patients were included in 2010–2013.

Results

In patients whose tumors expressed the KRAS wild type, the longest median OS was observed with irinotecan-based chemotherapy combined with bevacizumab (38 months), or with cetuximab (41 months). In the KRAS-mutated group, the longest median OS was observed with oxaliplatin with or without bevacizumab (34 months). Beneficial liver metastasis resections were observed in 12 out of 20 patients. Patients with KRAS wild-type tumors who received cetuximab were the most likely to undergo surgery. Age was a negative predictor of OS. Patients whose chemotherapy dose was reduced to below 80% had lower OS compared to those remaining above 80%. Treatment delays in chemotherapy did not affect OS. Pulmonary embolism and infections were common but did not have an impact on OS.

Conclusions

A hospital-based electronic informatics center provides comparable OS results, even though adverse events were frequently observed in the present study.

     

Non-oncology physician visits after diagnosis of cancer in adolescents and young adults

Purpose

Health care needs of adolescents and young adults (AYAs) with cancer are probably different from other age groups. Studying their non-oncology physician visits in the first years after diagnosis may provide insight into the specific health problems AYA patients experience and thereby help to improve care for these patients.

Methods

Seven hundred seventy-four AYAs identified from a Canadian provincial registry diagnosed with cancer between ages 15 and 24 years in 1991/2001 were included, matched by birth year and sex to ten controls. Based on provincial health insurance plan records, we determined the number of family physician and non-cancer specialist visits in the 5 years after diagnosis (for patients) or inclusion (for controls).

Results

The percentage of patients visiting a non-cancer specialist decreased from 96 to 49 % over the 5-year period. The percentage visiting a family physician decreased from 96 to 84 %. Visits in all years were significantly higher than among controls. In the first year after diagnosis, many patients visited a non-cancer specialist or a family physician for neoplasm-related health problems (77 and 55 %, respectively). In addition, family physicians were also consulted for general age-specific problems, such as genitourinary symptoms

Conclusions

In the first years after diagnosis of cancer in AYAs, both non-cancer specialist and family physician visits are common, although non-cancer specialist visits are less common and decline considerably faster than in younger children.

Implications for Cancer Survivors

The specific pattern of physician visits of this age group calls for care that is tailored to their specific needs.

     

Antiangiogenic effects in patients with progressive desmoplastic small round cell tumor: data from the French national registry dedicated to the use of off-labeled targeted therapy in sarcoma (OUTC’s)

Background

Desmoplastic small round cell tumor (DSRCT) is a very rare mesenchymal tumor that mainly affects teenagers and young adults with a mean age at diagnosis around 20–25 years. Although initial management still needs standardization, many centers will use multimodal treatment including intensive chemotherapy, extensive surgical resection followed by radiotherapy. Despite this, prognosis remains very poor and the median overall survival is 25 months. Recurrent disease is mainly treated by chemotherapy. Recently, due to the unmet medical need for recurrent disease, targeted therapies were explored for DSRCT.

Methods

In this study, we assessed the response rate and progression free survival in nine cases of progressive DSRCT included in the OUTC’s registry and treated with antiangiogenics targeted agents (sunitinib, sorafenib and bevacizumab). OUTC’s, a French national registry, collects data about the use of off-label targeted therapy in sarcoma.

Results

Eight males and one woman were included, with median age at diagnosis of 27.3 years (range from 9 to 48 years). They received a mean 3 lines (2–5) of treatment before antiangiogenic agent initiation. Six patients received sunitinib, two received sorafenib and one bevacizumab. Median progression free survival was 3.1 months (range 2–5.5 months) and best response observed was 5.5 months stable disease. Most patients had manageable low-grade toxicities, mainly fatigue, abdominal pain and skin toxicity.

Conclusions

Despite very limited activity of antiangiogenics in our study, prospective collection of cases of these rare tumors together with molecular data should guide therapeutic decision and enhance outcome.