Third-line Treatment Options Research Articles

Individualized medical treatment options in Cushing disease.

Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It is a serious endocrine disease associated with increased mortality and impaired quality of life. The management of CD remains challenging. Although transsphenoidal surgery is the treatment of choice in most cases, in approximately half of CD patients, second or third-line treatment options are needed. Currently, new medical therapies are available which target adrenal steroidogenesis, pituitary somatostatin and dopamine receptors, and glucocorticoid receptors. Selection of which medication to use should be individualized and is determined by many factors including severity of the disease, possible side effects, patients preferences and local availability. The aim of this article is to describe currently available medical therapy to help clinicians individualize the treatment options in the context of recently updated Pituitary Society recommendations.

A Clinical Guide to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in Neuroendocrine Tumor Patients

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-[DOTA0,Tyr3]-octreotate (177Lu-DOTATATE) has become an established second- or third-line treatment option for patients with somatostatin receptor (SSTR)-positive advanced well-differentiated gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). Clinical evidence of the efficacy of PRRT in tumor control has been proven and lower risks of disease progression or death are seen combined with an improved quality of life. When appropriate patient selection is performed, PRRT is accompanied by limited risks for renal and hematological toxicities. Treatment of NET patients with PRRT requires dedicated clinical expertise due to the biological characteristics of PRRT and specific characteristics of NET patients. This review provides an overview for clinicians dealing with NET on the history, molecular characteristics, efficacy, toxicity and relevant clinical specifics of PRRT.

Asciminib (Scemblix): A third-line treatment option for chronic myeloid leukemia in chronic phase with or without T315I mutation.

To review the pharmacology, efficacy, safety, dosing and administration, and place in therapy of asciminib, an oral tyrosine kinase inhibitor (TKI) used as a third-line treatment option for Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase. CML is a rare cancer caused by a chromosomal translocation that forms a fusion of the BCR and ABL1 genes on chromosomes 22 and 9. Until recently, patients for whom first-line treatment options failed were treated with TKIs that bind to the adenosine triphosphate-binding site on BCR-ABL1. However, because of similar mechanisms of action, there continues to be an unmet need in patients for whom at least 2 TKIs have failed or those with a T315I mutation unable to tolerate ponatinib. In October 2021, the Food and Drug Administration approved asciminib (Scemblix), the first TKI specifically targeting the ABL1 myristoyl pocket (STAMP) via allosteric binding, as a third-line option for patients with chronic-phase (CP)-CML. Asciminib received accelerated approval due to meeting its primary endpoint at week 24, demonstrating a major molecular response rate of 25.5% for patients on asciminib compared to 13.2% for those receiving bosutinib. In addition, patients on asciminib achieved a higher rate of complete cytogenetic response at 40.8% compared to a rate of 24.2% for bosutinib. Clinicians prescribing asciminib should monitor for increased levels of pancreatic enzymes, hypertension, cardiovascular toxicity including ischemic and thromboembolic conditions, and decreased numbers of neutrophils and platelets, as these may require treatment interruption, dose reduction, or treatment discontinuation. Asciminib is a unique targeted TKI that provides clinicians with an additional third-line and beyond treatment option for adults with CP-CML regardless of mutation status as well as a second TKI treatment option for patients harboring a T315I mutation.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p < 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity towarda specific type of treatment can aid with individualized counseling on third-line OAB therapies.

Omalizumab for the management of refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a heterogeneous, systemic, primarily mast cell-driven disease with sudden appearance of wheals with or without angioedema with pruritus for more than 6 weeks. It affects 0.3%–0.6% of the general population. CSU is a complex immune-mediated disease due to induction of basophil and mast cell degranulation with more than one mechanism of auto-allergy Type I (mediated by specific immunoglobulin E (IgE) targeting auto-allergens as thyroperoxidase, etc.) and auto-immunity Type II (mediated by IgG auto-antibodies binding to alpha-subunit of high affinity IgE receptor [FcERI]) with increased expression of Type II cytokines and activation of coagulation cascade. Pruritus is due to sensory nerve activation by histaminergic pathway (Histamine receptors- H1R and H4R) and histamine-independent pathway (Substance P, Capsacin, and Reactive oxygen species, etc.). The international guidelines on CSU recommend to treat CSU until it is gone. The use of second-generation anti-histamine in effective dose as the first-line treatment and up-dosing of second generation (SgAH) up to four-fold is recommended in treatment-resistant patients. The humanized anti-IgE monoclonal antibody Omalizumab has been shown to have both excellent safety profiles as the only third-line treatment option in anti-histamine-resistant urticaria (approved by United States Food and Drug Administration in August, 2014). However, there are several questions to be answered with reference to the optimal dose, duration, and the rates of long-term remission with omalizumab. Other biologics as Ligelizumab are less well studied but have an important role in the specific type of omalizumab-resistant CSU. In this review, we will summarize the role of omalizumab in anti-histamine resistant CSU.

Real-World Treatment with Nivolumab or Cabozantinib for Metastatic Renal Cell Carcinoma (mRCC) in the Veneto Region of Italy: Results of AMOUR Study

BackgroundSecond- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials.ObjectiveWe conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system.Patients and MethodsWe conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017–2018 at 19 Oncology Units in the Veneto Region.ResultsWe identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR > 3 had a shorter OS (p < 0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumab>cabozantinib sequence versus cabozantinib > nivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumab > cabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80.ConclusionsIn our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective.

Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.

4072 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the Phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥ 1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]

Combination and Novel Pharmacologic Agents for OAB.

To evaluate recent literature on combination and novel pharmacologic therapies for overactive bladder (OAB). Combination therapies demonstrating greater efficacy than monotherapy include combination anticholinergics, anticholinergic plus β-3 agonist, and anticholinergic with behavioral modification, percutaneous tibial nerve stimulation, or sacral neuromodulation. Promising novel therapies include new bladder selective anticholinergics, new β-3 agonists, and gabapentin. OAB is a symptom complex caused by dysfunction in the interconnected neural, muscular, and urothelial systems that control micturition. Although several therapeutic targets and treatment options exist, complete resolution is not always achieved, discontinuation rate for medical therapy is high, and few patients subsequently progress to third-line treatment options. Recent literature suggests combination therapy diversifying therapeutic targets is more effective than targeting a single pathway and novel treatments targeting additional pathways have promising results.

Peripheral Neuropathies Derived from COVID-19: New Perspectives for Treatment.

Peripheral neuropathies constitute a group of disorders affecting the peripheral nervous system. Neuropathies have multiple causes such as infections (i.e., COVID-19), diabetes, and nutritional (low vitamin levels), among others. Many micronutrients, such as vitamins (A, C, D, E, B6, B12, and folate), certain minerals (Fe, Mg, Zn, Se, and Cu), and ω-3 fatty acids have immunomodulatory effects. Therefore, they may play an instrumental role in the treatment of COVID-19 infection. However, many COVID-19 patients can undergo neuropathy. In this context, there is a wealth of information on a variety of first-, second-, and third-line treatment options. This review focuses on the application of nutraceutical strategies in order to improve the symptomatology of neuropathy and neuropathic pain in patients that suffered from COVID-19. Our aim is to provide an alternative vision to traditional medical-pharmacological treatment through nutraceuticals.

Status epilepticus: review on diagnosis, monitoring and treatment.

Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either from the failure of the mechanisms responsible for seizure termination or initiation, leading to abnormally prolonged seizures. The definition has different time points for convulsive, focal and absence SE. Time is brain. There are changes in synaptic receptors leading to a more proconvulsant state and increased risk of brain lesion and sequelae with long duration. Management of SE must include three pillars: stop seizures, stabilize patients to avoid secondary lesions and treat underlying causes. Convulsive SE is defined after 5 minutes and is a major emergency. Benzodiazepines are the initial treatment, and should be given fast and an adequate dose. Phenytoin/fosphenytoin, levetiracetam and valproic acid are evidence choices for second line treatment. If SE persists, anesthetic drugs are probably the best option for third line treatment, despite lack of evidence. Midazolam is usually the best initial choice and barbiturates should be considered for refractory cases. Nonconvulsive status epilepticus has a similar initial approach, with benzodiazepines and second line intravenous (IV) agents, but after that, aggressiveness should be balanced considering risk of lesion due to seizures and medical complications caused by aggressive treatment. Usually, the best approach is the use of sequential IV antiepileptic drugs (oral/tube are options if IV options are not available). EEG monitoring is crucial for diagnosis of nonconvulsive SE, after initial control of convulsive SE and treatment control. Institutional protocols are advised to improve care.

IDF21-0645 SOLUTION study: Effect of gemigliptin as add-on therapy to dapagliflozin plus metformin in patients with type 2 diabetes

Background: As type 2 diabetes mellitus (T2DM) is a complex disease, the glycaemic control can be more difficult as time of diabetes duration goes on. Gemigliptin, when used as monotherapy or and an add-on to metformin therapy in patient with inadequately controlled T2DM, improved glycemic control with sound safety. Therefore, in T2DM patients who are not adequately controlled with sodium-glucose cotransporter-2 (SGLT2) inhibitor plus metformin, gemigliptin, a kind of dipeptidyl peptidase-4 (DPP-4) inhibitors, can be considered as additional third-line treatment option.

Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.

420 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review.

ObjectiveThe efficacy and safety of regorafenib and fruquintinib are studied extensively in different populations and trials across the world to determine their potential benefits. Here we review the efficacy and safety of regorafenib and fruquintinib as third-line treatment option for colorectal cancer (CRC).BackgroundCRC is the third most prevalent cancer worldwide, but the optimal third-line treatment option is still debatable. Regorafenib is a multikinase inhibitor that inhibits several cell signaling receptors, including vascular endothelial growth factor receptors (-1, -2, and -3) (VEGFRs), platelet-derived growth factor (PDGF), fibroblast growth factor, epidermal growth factor (EGF), angiotensin II, and Rapidly Accelerated Fibrosarcoma kinase pathway. On the other hand, fruquintinib inhibits signaling through the VEGFRs family. Regorafenib and fruquintinib have both received United States Food and Drug Administration (USFDA) approval for treating metastatic CRC (mCRC) in patients previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti- vascular endothelial growth factor therapy, and Rat sarcoma wild type, an anti- EGF receptor therapy.MethodsA review of literature was conducted in PubMed and Embase with the keywords “regorafenib” OR “fruquintinib” AND “colorectal cancer” for clinical studies performed in randomized controlled settings and real-world settings.ConclusionsRegorafenib and fruquintinib are effective and well tolerated options for the third-line treatment of patients with CRC. Both have a similar survival outcome with Regorafenib showing a slightly better toxicity profile.

British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective. provide guideline recommendations and if appropriate research recommendations.

Prevalence and Medications of Atopic Dermatitis in Germany: Claims Data Analysis.

BackgroundInformation on the prevalence of atopic dermatitis (AD) varies greatly, and so far, only a few studies describe the healthcare of patients with AD in Germany.ObjectiveThe aim of the study is to describe the prevalence and medications of people with AD in Germany.MethodsHealth insurance data for the year 2019 were examined. Prevalence rates, the severity of disease, comorbidities and pharmaceutical supply were analyzed. Insured persons with AD were identified with at least one outpatient or inpatient International Classification Code of Diseases (L20).ResultsIn 2019, 4.21% [95% CI 4.21−4.22%] of insured persons had AD (3.6 million). Women were affected slightly more frequently than men (4.74% [95% CI 4.73−4.74%] and 3.64% [95% CI 3.64−3.65%]). Adolescents and children under the age of 15 had the highest prevalence of AD compared to other age groups (9.44% [95% CI 9.42−9.46%]). Majority of the insured persons with AD were affected by a mild to moderate form of the disease. The most common co-morbidity was infections of the skin (RR 5.00 [95% CI 4.97−5.02%]). Some patients were treated by a dermatologist, while others by a general practitioner, 39.10% and 36.74%, respectively. Of the anti-inflammatory drugs, systemic glucocorticosteroids preparations were used most frequently and were most frequently prescribed by the general practitioner. With a total of 42,841 prescriptions (1.53%), methotrexate (third-line treatment option) was prescribed more frequently than ciclosporin with 19,628 prescriptions (0.70%) or azathioprine with 25,696 prescriptions (0.92%). Ciclosporin (first-line treatment option) was prescribed much more frequently by a dermatologist (44.00% versus 14.32% by general practitioner). The biological dupilumab was prescribed 30,801 times (1,10%) and was also primarily prescribed by a dermatologist (66.67%).ConclusionThe present results reveal that a specialist treats approximately one-third of the patients with AD and that there is still a drug undersupply in some cases, especially concerning innovative drugs.

Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis

BackgroundTumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an...

Treatment outcomes of erlotinib plus gemcitabine as late-line chemotherapy in unresectable pancreatic cancer.

With the introduction of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy for unresectable pancreatic cancer, erlotinib plus gemcitabine therapy is now occasionally used as late-line therapy. This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer. We retrospectively analysed consecutive patients with unresectable pancreatic cancer treated with erlotinib plus gemcitabine as the third or later-line chemotherapy between March 2014 and December 2020 in our hospital. A total of 56 patients were included (third line/fourth or later line = 42/14). All patients were previously treated with gemcitabine plus nab-paclitaxel and 45 patients were previously treated with modified FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 1.6 and 4.6 months, respectively. The disease control rate was 21.4%. Performance status, modified Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify patients into good (n = 32) and poor (n = 24) prognostic groups. The median PFS and OS were longer in good than in poor prognostic group, but the difference in PFS was very small (PFS: 2.1 vs. 1.4 months, P = 0.01. OS: 6.8 vs. 2.4 months, P < 0.01). Interstitial pneumonia occurred in one patient (1.8%). Benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. Development of more effective third-line treatment options is desirable in the future.

Selection of Oral Therapeutics in China for the Treatment of Colorectal Cancer.

Intravenous administration of fluoropyrimidine-based chemotherapy has been the backbone of treatment in colorectal cancer (CRC) for decades. The availability of oral capecitabine has improved the tolerability and simplified combination schedules. In addition to capecitabine, several other oral drugs have proven efficacy, particularly in palliative treatment lines. Clinical guidelines describe several available third-line treatment options for metastatic CRC (mCRC), but few insights are provided to guide the selection and sequence. In this review, we describe the available evidence and most recent data concerning oral drugs with proven efficacy in CRC, including antiangiogenetic tyrosine kinase inhibitors (VEGFR TKIs), inhibitors blocking EGFR/Raf/MEK/ERK signaling pathway and modified fluoropyrimidine, and share recommendations and insights on selecting third-line oral therapies for mCRC in China. In general, third-line treatment options for mCRC are mainly regorafenib, fruquintinib, and chemo/targeted therapy reintroduction, while FTD/TPI was rarely used in China probably due to poor accessibility. Fruquintinib is preferred in patients with poor performance status (PS), elder age, and severe organ dysfunction, compared to regorafenib. New drugs of clinical trials were more recommended for the patients with BRAF mutant tumor, and those with good previous treatment efficacy tended to be recommended for chemo/targeted therapy reintroduction. The management of mCRC is evolving, and it must be emphasized that the consideration and recommendations presented here reflect current treatment practices in China and thus might change according to new clinical data as well as the availability of new oral drugs.

Biomarker-Oriented Therapy in Bladder and Renal Cancer.

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor—tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.

Use of nivolumab (N) and cabozantinib (C) for treatment of the metastatic renal cell carcinoma (mRCC) in the Veneto region: Results of AMOUR study.

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR &gt; 3 at treatment start had a shorter OS (43 vs 90 months (mos), p &lt; 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N &gt; C, 12 the opposite sequence C &gt; N. Median OS for N &gt; C vs C &gt; N were 96.6 vs 36 mos (p &gt; 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N &gt; C is 51.606 € while for the sequence C &gt; N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N &gt; C was 534,18 € while for the sequence C &gt; N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N &gt; C appear to be a better treatment strategy.