Treatment patterns in advanced/metastatic non-small-cell lung cancer in China: results from the CancerMPact® survey 2021.

Aim: To report the treatment patterns of advanced/metastatic non-small-cell lung cancer (NSCLC) in China from a physician survey (CancerMPact®). Materials & methods: A total of 206 Chinese physicians from 27 cities in urban mainland China reported on their treatment of NSCLC in September 2021. Results: Platinum doublets received 70.5% utilization for squamous NSCLC with PD-L1 expression <1% in first-line, whereas nonsquamous NSCLC was treated with platinum doublets (35.2%) or bevacizumab with platinum doublets (35.3%). Checkpoint inhibitors were utilized in >50% of all PD-L1-positive NSCLC cases. Driver-mutated NSCLC was most frequently treated with targeted therapy or platinum-based combinations. Conclusion: NSCLC treatment in China varies by histology, PD-L1 status and driver mutations, illustrating the complexity of decision-making for Chinese physicians as treatment markets expand.

The most common type of lung cancer is called non-small-cell lung cancer (NSCLC). When lung cancer spreads beyond the lung, it is called advanced. Doctors in China who treat advanced NSCLC were identified. They were surveyed in September 2021 and asked about how they treat their patients. The survey included 206 doctors from 27 cities in China. There are many drugs available for NSCLC. This means that it can be hard for doctors to decide how to treat their patients. The doctors in China often reported using multiple drugs together, instead of using only one drug. One type of drug that can be used to treat NSCLC is called a checkpoint inhibitor (CPI). The doctors reported that they often used CPIs to treat their patients. They also reported that they were more likely to use CPIs made in China rather than CPIs that were made outside of China. Before receiving treatment, most patients were tested for biomarkers. Biomarkers can tell doctors important information about cancers. Doctors can use biomarkers to help decide which treatments to offer their patients. In China, the doctors often did use certain drugs based on patient biomarkers. This choice often depended on the specific biomarker that the patient had. There are many different factors for doctors to consider when treating NSCLC. More and more drugs are becoming available to use in China. While this is good news for patients with cancer, treatment decisions are becoming more complex for doctors.

Physician reported treatment patterns and outcomes in metastatic bladder cancer in the USA: the CancerMPact® Survey 2020.

Aim: This study assessed physician-reported treatment patterns for metastatic bladder cancer. Materials & methods: A total of 106 USA-based physicians were surveyed in 2020 using the CancerMPact® online survey. Results: Among cisplatin-eligible patients, 86.1% received first-line (1L) platinum-containing chemotherapy, most commonly cisplatin plus gemcitabine, and 9.8% received immune checkpoint inhibitor monotherapy. Among cisplatin-ineligible patients, 46.5% received 1L platinum-containing chemotherapy, most commonly carboplatin plus gemcitabine and 46.2% received 1L immune checkpoint inhibitor therapy. Approximately 44% of patients who received 1L treatment received second-line (2L) therapy after progression. Conclusion: Platinum-containing chemotherapy was the most widely reported 1L treatment approach. A high proportion of patients received no 2L therapy. Validation in an updated dataset is warranted following the practice-changing approvals of avelumab 1L maintenance and additional 2L options.

In 2020, researchers surveyed 106 US doctors about how they treated people with advanced bladder cancer. Cisplatin, a chemotherapy drug, was the most common first treatment that was given to patients with advanced bladder cancer. For people who were unable to receive cisplatin, doctors preferred to prescribe a similar chemotherapy drug called carboplatin or an immunotherapy drug. Immunotherapies help the body's immune system to fight cancer cells. Most people treated by the surveyed doctors did not receive a second treatment if their cancer got worse. New treatments are now available for bladder cancer, such as the immunotherapy, avelumab. Avelumab is given after chemotherapy to try and stop the cancer from getting worse or coming back. More research is needed to further understand how bladder cancer is treated.

Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Metastatic non-small-cell lung cancer without driver mutations: projections by therapy line in Western Europe, 2021-2026.

Aim: To estimate the incidence, prevalence and treated prevalence by line of therapy (LOT) for non-small-cell lung cancer (NSCLC) patients without driver mutations from 2021 to 2026. Materials & methods: Country-specific registry data for Western Europe were used to project incidence and prevalence of NSCLC; LOT information was obtained from CancerMPact® Treatment Architecture physician surveys. Results: Incidence, prevalence and treated prevalence across LOTs for NSCLC are projected to increase across five WE countries, including for stage IV patients without driver mutations (184,966 cases [2021] to 197,925 [2026]). Pembrolizumab monotherapy is utilized by ∼50% of NSCLC patients with programmed death-ligand 1 expression ≥50%. Conclusion: Improved treatment options for NSCLC patients without known driver mutations are important for combating the projected increase in prevalence.

Lung cancer is the leading cause of cancer-related death in Europe. This study estimated how the number of patients living with, and being treated for, lung cancer is projected to change between 2021 and 2026 in Western Europe by collecting past data on lung cancer in France, Germany, Italy, Spain and the UK, and analyzing the trends to create estimates for the future. The number of new cases of lung cancer is projected to increase each year from 2021 to 2026, and in line with this, the number of patients receiving treatment for their disease will increase. Improving treatment options for lung cancer will be an important step to combat the expected increase in cancer cases.

Treatment of HR+/HER2- breast cancer in urban mainland China: results from the CancerMPact Survey 2019.

PURPOSE: To report the treatment utilization patterns for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer in urban mainland China (CancerMPact®). METHODS: The results presented are from an online survey conducted in September 2019 with 45 physicians treating breast cancer patients from 11 cities in mainland China. RESULTS: Surveyed physicians reported that Stage I HR+/HER2(-) breast cancer patients are often treated with surgery alone (42%), whereas the use of surgery in combination with systemic therapy with or without radiotherapy increases in later stages (Stage II 67%, Stage III 77%). Doxorubicin-cyclophosphamide (AC)-based regimens were the most common in both the neoadjuvant and adjuvant settings in HR+/HER2(-) breast cancer patients, across all stages. In metastatic patients, use of surgery and radiotherapy decreases in favor of utilization of systemic therapy alone. Pre- and post-menopausal metastatic patients were frequently treated with hormone therapy or AC-based regimens in first line. Regardless of the first-line therapy administered, capecitabine-based regimens were commonly used in second line. In third line, chemotherapy regimens containing capecitabine or gemcitabine were given to nearly 40% of HR+/HER2(-) breast cancer patients. There were no standard of care regimens established for fourth or greater lines of treatment. In metastatic HR+/HER2(-) breast cancer, physicians reported 50% objective response rates in first-line settings with a progression-free survival of 16 months. CONCLUSION: HR+/HER2(-) breast cancer patients in urban mainland China were prescribed chemotherapy regimens more frequently than CDK4/6 inhibitors. Treatment practices varied, with physicians reporting the use of multiple modalities and treatment regimens for their patients.

Estimate of multiple myeloma patients by line of therapy in the USA: population-level projections 2020-2025.

Aim: To report the results of a patient epidemiology model for multiple myeloma (MM) treatment by line of therapy (LOT) in the USA. Materials & methods: Surveillance, Epidemiology and End Results registry data and physician surveys were combined to project the incidence, prevalence and the number of MM patients treated with systemic therapy by LOT between 2020 and 2025. Results: Projected complete MM prevalence in the USA in 2020 was 144,922, increasing to 162,339 in 2025. Corresponding unique MM patients by LOT in 2020 were: 53,176 (1st; minimum-maximum: 47,304-59,212), 19,407 (2nd; 15,935-23,273), 6,481 (3rd; 5143-8877), 1649 (4th; 1146-2667) and 426 (5th; 217-876). Conclusion: MM incidence and prevalence by LOT is projected to continue to increase in the USA between 2020 and 2025.

Treatment patterns in non-small-cell lung cancer in USA: results of the CancerMPact Survey 2018.

Aim: To report the results of a survey of USA physicians (CancerMPact) that treat non-small-cell lung cancer patients. Materials & methods: 60 physicians were surveyed. Questions covered aspects of the treatment for all stages of the disease. Results: For stage I patients, over 70% of the treatments were based on surgery. For stage II/III disease, a strong preference for combined therapy (surgery/radiation/systemic therapy) was observed. For advanced/stage IV patients, physicians used systemic therapy alone, and choosed the regimen based on histology and biomarkers. Use of PD-L1 inhibitors was highly dependent on histology and biomarkers. Conclusion: The treatment choices of non-small-cell lung cancer are increasingly complex, involve different treatment modalities and are highly dependent on histology and biomarkers, besides stage.

WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. OBJECTIVES: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. SEARCH METHODS: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. SELECTION CRITERIA: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. MAIN RESULTS: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. AUTHORS' CONCLUSIONS: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). RESULTS: The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). CONCLUSION: The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

BACKGROUND: Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. OBJECTIVES: To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. SEARCH METHODS: We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. SELECTION CRITERIA: We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. MAIN RESULTS: Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. AUTHORS' CONCLUSIONS: The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis.

BACKGROUND: Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%). RESULTS: The final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26). CONCLUSION: Overall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.

Systematic review and meta-analysis of target terapies for the treatment of metastatic renal cancer.

OBJECTIVES: At present there are several drugs for the treatment of advanced renal cell carcinoma (ARCC). The main objective of this work was to perform a systematic review (SR) and meta-analysis (MA) of clinical randomized studies that compared target cell therapies (TCT). MATERIALS AND METHODS: SR identified clinical randomized trials that compared TCT versus interferon-alpha in the treatment of patients with ARCC. In order to analyze efficiency, it was evaluated free-survival progression (FSP), total survival (TS) and response rate (RR). RESULTS: In relation to first line treatment, seven studies of TCT were identified using sunitinib, sorafenib, bevacizumab and temsirolimus; and two studies with sorafenib and everolimus for second line treatment. Relative risk (RRi) of MA for FSP of first line therapies was: 0.83, CI = 0.78-0.87, I2 = 94% and p < 0.00001. Best results of RR of specific FSP among studies were: 0.38, sunitinib, CI = 0.25-0.58, bevacizumab, 0.62, CI = 0.47-0.83; and temsirolimus, 0.78, CI = 0.70-0.87. MA didn't show any benefit regarding TS of first line treatment of all analyzed drugs. As for RR significant results were: sunitinib, 3.83 CI = 2.86-5.12; bevacizumab, 2.52 CI = 1.78-3.57 and bevacizumab, 1.97 CI = 1.43-2.71. CONCLUSIONS: For first line treatment, sunitinib was the most effective TCT in relation to FPS; there was no alteration of TS and RR was small but significant for sunitinib and bevacizumab. Available studies could not conclude any results for second line treatments.

Bisphosphonates in multiple myeloma: a network meta-analysis.

BACKGROUND: Bisphosphonates are specific inhibitors of osteoclastic activity and used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010. OBJECTIVES: To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus nonamino bisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression-free survival (PFS), and decreases skeletal-related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw and hypocalcemia. SEARCH METHODS: We searched MEDLINE, LILACS, EMBASE (December 2009 to October 2011) and the Cochrane Controlled Trials Register (all years, latest Issue September 2011) to identify all randomized trials in MM up to October 2011 using a combination of text and MeSH terms. We also handsearched relevant meeting proceedings (December 2009 to October 2011). SELECTION CRITERIA: Any randomized controlled trial (RCT) assessing the role of bisphosphonates and observational studies or case reports examining bisphosphonate-related osteonecrosis of the jaw in patients with MM were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) under a random-effects model. Statistical heterogeneity was explored using metaregression. MAIN RESULTS: In this update, we included 2 studies (2464 patients) that were not part of our last Cochrane review published in 2010. In this review we included 16 RCTs comparing bisphosphonates with either placebo or no treatment and 4 RCTs with a different bisphosphonate as a comparator. The 20 included RCTs enrolled 6692 patients. Overall methodological quality of reporting was moderate. Thirty per cent (6/20) of trials reported the method of generating the randomization sequence. Forty per cent (8/20) of trials had adequate allocation concealment. Withdrawals and dropouts were described in 60% (12/20) of trials. Pooled results showed no direct effect of bisphosphonates on OS compared with placebo or no treatment (HR 0.96, 95% CI 0.82 to 1.13; P = 0.64). However, there was a statistically significant heterogeneity among the included RCTs (I(2) = 55%, P = 0.01) for OS. To explain this heterogeneity we performed a metaregression assessing the relationship between bisphosphonate potency and improvement in OS, which found indicating an OS benefit with zoledronate (P = 0.058). This provided a further rationale for performing network meta-analyses of the various types of bisphosphonates that were not compared head to head in RCTs. Results from network meta-analyses showed superior OS with zoledronate compared with etidronate (HR 0.43, 95% CI 0.16 to 0.86) and placebo (HR 0.61, 95% CI 0.28 to 0.98). However, there was no difference between zoledronate and other bisphosphonates. Pooled analysis did not demonstrate a beneficial effect of bisphosphonates compared with placebo or no treatment in improving PFS (HR 0.70, 95% CI 0.41 to 1.19; P = 0.18) There was no heterogeneity among trials reporting PFS estimates (I(2) = 35%, P = 0.20).Pooled analysis demonstrated a beneficial effect of bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; I(2) = 7%), skeletal-related events (SRE) (RR 0.80, 95% CI 0.72 to 0.89; I(2) = 2%) and amelioration of pain (RR 0.75, 95% CI 0.60 to 0.95; I(2) = 63%). The network meta-analysis did not show any difference in the incidence of osteonecrosis of the jaw (5 RCTs, 3198 patients) between bisphosphonates. Rates of osteonecrosis of the jaw in observational studies (9 studies, 1400 patients) ranged from 0% to 51%. The pooled results (6 RCTs, 1689 patients) showed no statistically significant increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.60; P = 0.11).The pooled results (3 RCTs, 1002 patients) showed no statistically significant increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74). The network meta-analysis did not show any differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used. AUTHORS' CONCLUSIONS: Use of bisphosphonates in patients with MM reduces pathological vertebral fractures, SREs and pain. Assuming a baseline risk of 20% to 50% for vertebral fracture without treatment, between 8 and 20 MM patients should be treated to prevent vertebral fracture(s) in one patient. Assuming a baseline risk of 31% to 76% for pain amelioration without treatment, between 5 and 13 MM patients should be treated to reduce pain in one patient. With a baseline risk of 35% to 86% for SREs without treatment, between 6 and 15 MM patients should be treated to prevent SRE(s) in one patient. Overall, there were no significant adverse effects associated with the administration of bisphosphonates identified in the included RCTs. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or nonaminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate appears to be superior to placebo and etidronate in improving OS.

Immunotherapy with Sipuleucel-T (APC8015) in patients with metastatic castration-refractory prostate cancer (mCRPC): a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of Sipuleucel-T versus placebo for asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer (mCRPC). MATERIALS AND METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), time to progression (TTP) and side effects. We performed a meta-analysis (MA) of the published data. The results are expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% confidence intervals (CI 95%). RESULTS: The final analysis included 3 trials comprising 737 patients. The TTP was similar in patients who received Sipuleucel-T or placebo (fixed effect: HR = 0.89; CI 95% = 0.75 to 1.05; p = 0.16), with no heterogeneity detected on this analysis (Chi2 = 2.14, df = 2 (P = 0.34); I2 = 6%). The results showed a higher overall survival in patients treated with Sipuleucel-T (fixed effect: HR = 0.74; CI 95% = 0.61 to 0.89; p = 0.001; NNT = 3). We found no heterogeneity on this analysis either (Chi2 = 1.46, df = 2 (P = 0.48); I2 = 0%). The incidence of adverse events (grade > 3) was the same in both groups. CONCLUSION: Sipuleucel-T prolongs overall survival in patients with asymptomatic or minimally symptomatic mCRPC.

Ideal vial size for bortezomib: real-world data on waste and cost reduction in treatment of multiple myeloma in Brazil.

OBJECTIVES: Single-size vials of drugs may be a source of waste and increase in treatment costs. Bortezomib, indicated for multiple myeloma (MM) treatment, is available in 3.5-mg vials, a quantity higher than the average dose commonly prescribed. This analysis aimed to demonstrate, through real-world data, which would be the optimal vial presentation for bortezomib in Brazil and quantify the reduction in medication waste related to this option. METHODS: From November 2007 to October 2009 all patients with MM treated with bortezomib were identified via the Evidências database. Analysis of prescribed, dispensed, and wasted doses, their costs and projections of the ideal vial size were performed. RESULTS: Thirty-five patients (mean body surface area of 1.73 m(2)) received 509 infusions in 131 cycles of treatment (average of 3.77 cycles per patient). The average dose prescribed was 2.1 mg per infusion (95% confidence interval [CI] 1.97-2.26) with average waste of 39.5% of the vial content (95% CI 35.35-43.76). The mean waste per patient per day was 1.38 mg (95% CI 1.24-1.52). If a 3-mg vial were available, the average drug waste per patient per day would be 0.88 mg (95% CI 0.74-1.03) or 36.2% less. With a 2.5-mg vial the waste would be 1.05 mg (95% CI 0.81-1.29) or 23.9% less. If two presentations were available (2.5 mg and 0.5 mg), the waste would be 0.52 mg (95% CI 0.4-0.63) or 62.5% less. Considering the price of the different vials to be proportional to the original 3.5-mg vial, the cost would be also reduced by the same rates described above. CONCLUSIONS: A simple adjustment in vial size may reduce the waste of bortezomib by 36% to 62% and can also reduce the cost of treatment.

Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis.

OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of palonosetron (PAL) 0.25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy. METHODS: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were the incidence of acute and delayed nausea and vomiting. The side effects of each treatment were analyzed. A subgroup analysis was performed to evaluate the influence of the use of corticosteroids. The results are expressed as risk ratio (RR) and the correspondent 95% confidence interval (CI). RESULTS: Five studies were included, with 2057 patients. PAL was compared with ondansetron, granisetron, and dolasetron. Patients in PAL group had less nausea, both acute (RR = 0.86; CI 95% = 0.76 to 0.96; p = 0.007) and delayed (RR = 0.82; CI95% = 0.75 to 0.89; p < 0.00001). They also had less acute vomiting (RR = 0.76; CI 95% = 0.66 to 0.88; p = 0.0002) and delayed vomiting (RR = 0.76; CI95% = 0.68 to 0.85; p < 0.00001). There were no statistical differences in side effects like headache (RR = 0.84; CI 95% = 0.61 to 1.17; p = 0.30), dizziness (RR = 0.40; CI 95% = 0.13 to 1.27; p = 0.12), constipation (RR = 1.29; CI 95% = 0.77 to 2.17; p = 0.33) or diarrhea (RR = 0.67; CI 95% = 0.24 to 1.85; p = 0.44). Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids. We found no statistical heterogeneity in the global analysis. CONCLUSION: PAL was more effective than the other 5-HT(3)R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids.

Antibiotic prophylaxis for transrectal prostate biopsy.

BACKGROUND: Transrectal prostate biopsy (TRPB) is a well established procedure used to obtain tissue for the histological diagnosis of carcinoma of the prostate. Despite the fact that TRPB is generally considered a safe procedure, it may be accompanied by traumatic and infective complications, including asymptomatic bacteriuria (bacteria in the urine), urinary tract infection (UTI), transitory bacteremia (bacteria in the blood), fever episodes, and sepsis (pathogenic microorganisms or their toxins in the blood). Although infective complications after TRPB are well known, there is uncertainty about the necessity and effectiveness of routine prophylactic antibiotics and their adverse effects, as well as a clear lack of standardization. OBJECTIVES: To evaluate the effectiveness and adverse effects of prophylactic antibiotic treatment in TRPB. SEARCH STRATEGY: The search covered the principal electronic databases: MEDLINE, EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL). Experts were consulted and references from the relevant articles were scanned. SELECTION CRITERIA: All randomized, controlled trials (RCTs) of men who underwent TRPB and received prophylactic antibiotics or placebo/no treatment, were selected, and all RCTs looking at one type of antibiotic versus another, including comparable dosages, routes of administration, frequency of administration, and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS: Two reviewers (ELZ, OACC) independently selected included trials and extracted study data. Any disagreements were resolved by a third party (NRNJ). MAIN RESULTS: Overall, more than 3500 references were considered and 19 original reports with a total of 3599 patients were included.There were 9 trials analysing antibiotics versus placebo/no treatment, with all outcomes significantly favouring antibiotic use (P < 0.05) (I(2) = 0%), including bacteriuria (risk ratio (RR) 0.25 (95% confidence interval (CI) 0.15 to 0.42), bacteremia (RR 0.67, 95% CI 0.49 to 0.92), fever (RR 0.39, 95% CI 0.23 to 0.64), urinary tract infection (RR 0.37, 95% CI 0.22 to 0.62), and hospitalization (RR 0.13, 95% CI 0.03 to 0.55). Several classes of antibiotics were effective prophylactically for TRPB, while the quinolones, with the highest number of studies (5) and patients (1188), were the best analysed. For 'antibiotics versus enema', we analysed four studies with a limited number of patients. The differences between groups for all outcomes were not significant. For 'antibiotic versus antibiotic + enema', only the risk of bacteremia (RR 0.25, 95% CI 0.08 to 0.75) was diminished in the 'antibiotic + enema group'. Seven trials reported the effects of short-course (1 day) versus long-course (3 days) antibiotics. Long course was significantly better than short-course treatment only for bacteriuria (RR 2.09, 95% CI 1.17 to 3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98, 95% CI 1.18 to 3.33). Comparing oral versus systemic administration - intramuscular injection (IM), or intravenous (IV) - of antibiotics, there were no significant differences in the groups for bacteriuria, fever, UTI and hospitalization. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Patterns of Care and Outcomes for Non-Metastatic Prostate Cancer in the United States: Results of the CancerMPact® Survey 2018.

PURPOSE: We describe patterns of care and treatment outcomes for non-metastatic PCa (nmPCA), either hormone-sensitive or castration-resistant, in the United States of America (USA) in 2018. METHODS: A survey (CancerMPact®) recruited physicians nationwide to answer an online questionnaire about how they treated patients with nmPCA. Questions covered aspects of treatment at all disease stages. Board-certified urologists and oncologists with at least five years of clinical practice and who treated at least 30 PCa patients monthly were included. RESULTS: The survey included responses from ninety-four physicians with an average of 17.5 years of clinical practice, who had treated a combined average of 4415 patients with nmPCA per month in 2018. Approximately 40% of patients in stage I were managed with either active surveillance or observation/no therapy, decreasing to 20%, 8% and 6% in stages II, III and IV(M0), respectively. Intensity-modulated radiotherapy was favored over other radiotherapy modalities, with rates of use ranging between 60% and 69% depending on disease stage. Leuprolide as monotherapy or in combination with enzalutamide, abiraterone or bicalutamide were the most common systemic treatment options for non-metastatic hormone-sensitive PCa (nmHSPC) patients with the first or second recurrence. Only 16.5% of non-metastatic castration-resistant PCa (nmCRPC) patients did not relapse within five years of initial therapy for nmCRPC. CONCLUSION: While PCa treatment recommendations are rapidly changing due to advances in treatment, we observed great concordance between their most current versions and real-world data treatment patterns reported by US physicians.

Treatment patterns in non-small-cell lung cancer in China: Results from the CancerMPact survey 2020.

PURPOSE: To report the treatment patterns of non-small-cell lung cancer (NSCLC) patients in China based on a survey of physicians (CancerMPact). METHODS: 117 Chinese physicians from 27 cities in mainland China were recruited for an online survey in October 2020, reporting on how they treat their patients across all disease stages, including histology and relevant biomarkers in advanced or metastatic NSCLC. RESULTS: Surveyed physicians indicated that almost half of their stage I patients were treated with surgery only. For stage II patients, it is more common to treat with surgery in combination with radiation and/or systemic therapy (44.5%), whereas the use of surgery decreases for stage III patients and the overall use of systemic therapy increases (63.4%-68.8%). Physicians are more likely to use systemic therapy alone for stage IV patients (31.4%). Chosen treatment regimens for stage IV NSCLC varied by histology and biomarkers, and several observed treatment patterns differed from the USA. In China, platinum-based chemotherapy is standard of care for treating stage IV NSCLC patients, unlike the USA, where checkpoint inhibitors are the dominant choice in first-line. Further, Chinese physicians reported prescribing biomarker-targeted agents for one-third or less of their patients with EGFR, ALK, ROS-1, or BRAF driver mutations, compared to 60-95% in the USA. CONCLUSION: As treatment options expand in NSCLC in China, physicians face complex decisions for the treatment of their patients. Treatment patterns often vary, including by disease histology and clinically relevant biomarkers. The standard of care for NSCLC in China also differs from the USA.

Bisphosphonates in multiple myeloma.

BACKGROUND: Bisphosphonates are specific inhibitors of osteoclastic activity and are currently used as supportive therapy for multiple myeloma (MM). However, the exact clinical role of bisphosphonates in MM remains unclear. OBJECTIVES: This update of the first review published in 2002. We have also analyzed observational studies targeting osteonecrosis of jaw (ONJ). SEARCH STRATEGY: We searched the literature using the methods outlined in the previous review. We also searched observational studies or case reports examining ONJ. SELECTION CRITERIA: We selected RCTs with a parallel design related to the use of bisphosphonate in myeloma. We also selected observational studies or case reports examining bisphosphonates related to ONJ. DATA COLLECTION AND ANALYSIS: We have reported pooled data using either hazard ratio or risk ratio and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. We have assessed statistical heterogeneity and reported I(2) statistic. MAIN RESULTS: This review includes 17 trials with 1520 patients analyzed in bisphosphonates groups, and 1490 analyzed in control groups. In comparison with placebo/no treatment, the pooled analysis demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures (RR= 0.74 (95% CI: 0.62 to 0.89), P = 0.001), total skeletal related events (SREs) (RR= 0.80 (95% CI: 0.72 to 0.89), P < 0.0001) and on amelioration of pain (RR = 0.75 (95% CI: 0.60 to 0.95), P = 0.01). We found no significant effect of bisphosphonates on overall survival (OS), progression-free survival (PFS), hypercalcemia or on the reduction of non-vertebral fractures. The indirect meta-analyses did not find the superiority of any particular type of bisphosphonate over others. Only two RCTs reported ONJ. The identified observational studies suggested that ONJ may be a common event (range: 0% to 51%). AUTHORS' CONCLUSIONS: Adding bisphosphonates to the treatment of MM reduces pathological vertebral fractures, SREs and pain but not mortality. Assuming the baseline risk of 20% to 50% for vertebral fracture without treatment, we estimate that between eight and 20 MM patients should be treated to prevent vertebral fracture(s) in one patient. Assuming the baseline risk of 31% to 76% for pain amelioration without treatment, we estimate that between five to 13 MM patients should be treated to reduce pain in one patient. Also, with the baseline risk of 35% to 86% for SREs without treatment, we estimate that between six and 15 MM patients should be treated to prevent SRE(s) in one patient. No bisphoshphonate appears to be superior to others.