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Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Results Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.

Aim: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. Methods: Multicenter, retrospective study. Results: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. Conclusion: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.

96 Background: Radium-223 represents an option for symptomatic metastatic castration-resistant prostate cancer (mCRPC) after demonstrated an overall survival improvement in the ALSYMPCA trial. Radium-223 real-life experiences are scarce, particularly after the results of the ERA-223 trial. To describe Radium-223 outcomes in real life practice, and specifically those related with bone health, sequence of treatment, and prognostic factors. Methods: Multicenter retrospective study of a cohort of 143 patients with mCRPC treated with Radium-223 in either the second line or third line of therapy or beyond in the context of routine clinical practice between 11 March 2013 and 26 July 2022, in seven Galician hospitals. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Between March 11, 2013, and July 26, 2022, 143 patients were enrolled from 5 Galician hospitals. With a median follow-up of 9.68 months. All patients signed an informed consent form agreeing to participate in this observational study, that was approved by the Galician Ethics Committee, registration code 2018/282. Results: Baseline patient and disease characteristics are summarized. Median follow-up was 9.68 months. Median overall survival (OS) was 12 months (95% CI 9.7 – 16.0). Best OS outcomes were achieved in second and third line, 18 months (95% CI 12.0 – 26.0) and 9.4 months (95% CI 8.0 – 12.0) months, respectively. Among those baseline clinic-analytical factors analyzed, only alkaline phosphatase level >354 UI/L was correlated with a worse OS (HR 2.56 (95% CI 1.39 – 4.72; p=0.003) and the number of cycles of Radium-223 received (HR 0.63 (95% CI 0.54 – 0.73; p

Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT.This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm). The primary endpoint was noninferiority of the experimental arm vs the standard arm in terms of overall survival (OS), based on a hazard ratio (HR) of lt; 1.3. Secondary endpoints included progression-free survival, overall response, safety, and quality of life (QOL).Between July 15, 2008, and July 5, 2013, 519 patients were recruited and started ICT; 407 patients received post-ICT treatment (cis+RT, n = 205; cet+RT, n = 202). At a median follow-up of 43.9 (cis+RT) and 41.1 (cet+RT) months, median OS was 63.6 and 42.9 months with cis+RT and cet+RT, respectively (HR [90% CI] = 1.106 [0.888-1.378], P =.4492). There were no differences in progression-free survival, overall response rates, or adverse event rates between groups. There was greater late neurotoxicity with cis+RT than cet+RT (P =.0058). Several QOL dimensions improved with cet+RT vs cis+RT (physical functioning, P =.0287; appetite loss, P =.0248; social contact, P =.0153).Noninferiority of cet+RT over cis+RT was not demonstrated.

Nanoparticles are being actively developed for biomolecular profiling of cancer biomarkers, tumor imaging in vivo, and targeted drug delivery. These nanotechnology-based techniques can be applied widely in the management of different malignant diseases, such as breast cancer. Although the number of different types of nanoparticles is increasing rapidly, most can be classified into two major types: particles that contain organic molecules as a major building material (such as dendrimers, micelles, liposomes and carbon nanotubes, and other polymers); and those that use inorganic elements, usually metals, as a core. In particular, inorganic nanoparticles have received increased attention in the recent past as potential diagnostic and therapeutic systems in the field of oncology. This review primarily discusses progress in applications of inorganic nanoparticles for breast cancer imaging and treatment.

Prostate cancer is the most frequent cancer amongst men. Until recently, only two therapeutic options, initial androgen-deprivation therapy in patients without castration-resistant prostate cancer, with addition of docetaxel when the disease becomes castration-resistant, were considered as standard. In the last years, new drugs (abiraterone, enzalutamide, Ra-223, Sipuleucel) have been developed for prostate cancer treatment with important advantages in safety and efficacy. Results from the recent Chaarted study, in patients that received docetaxel for the hormone sensitive disease, have contributed to change the initial treatment approach in metastatic prostate cancer, in order to adapt the best sequence for each patient. Those results have been supported by the Stampede trial. Stampede survival data showed not only a benefit in overall survival of adding docetaxel initially, but also a prolonged time to first skeletal related event. Now it is discussed in which setting the available drugs should be administered. This review article summarizes the treatment options for patients treated with docetaxel initially for hormone sensitive prostate cancer after developing progressive disease, and offers an algorithm proposal for treatment.

e20579 Background: The current treatment of advanced non-small cell lung cancer (NSCLC) is conditioned by the presence of molecular and immunohistochemical biomarkers. In the absence of these, the therapeutic option is the use of chemotherapy with or without antiangiogenic agents. The efficacy of non-target systemic treatments is not proven, beyond a second-line and the experiences in their use are limited to retrospective analyzes. We present the experience of the Grupo Gallego de Cáncer de Pulmón in patients with advanced NSCLC treated exclusively with three or more lines of chemotherapy. Methods: Retrospective analysis of patients with advanced NSCLC, treated with three or more lines of chemotherapy in standard regimen, with or without antiangiogenic agents, in Galicia´s hospitals, Spain. Results: We included 168 patients (134 male and 34 female) treated with three or more chemotherapy lines, with a median age at the time of receiving the first-line, of 60.84 years (41-83). Of these, 51 (30,35%) received a fourth-line and 18 (10,74%) a fifth-line of treatment. None received antitarget therapy or immunotherapy. The median overall survival (OS) was 18.1 months. The median OS after the third line was 6.1 months, with 73% of patients alive at three months and 44% six months after the start of that therapeutic line. We did not appreciate differences in OS between those who received three lines and those who received the largest number of subsequent treatments. Our multivariate analysis (age, gender, histology, performance status at initiation of each teatment-line, response to previous treatments) identified that the individuals who benefited the most were those under the age of 60 years, PS-ECOG 0-1 at diagnosis and those with a more durable response to the first-line. Conclusions: The third-line of chemotherapy can benefit those patients with advanced NSCLC, under 60 years of age at the time of diagnosis, with good performance status and with long-lasting responses to the first line of treatment. We did not see benefit in adding fourth or fifth-line of chemotherapy. All data will be presented in the 2019 ASCO annual meeting.

e20645 Background: The lung immune prognostic index (LIPI) has been proposed as a new biomarker to select advanced non-small cell lung cancer (NSCLC) patients for anti-programmed cell death-1 or programmed death ligand 1 therapy. In this study, we investigate the prognostic and predictive utility of the LIPI in a multicentric nivolumab monotherapy-based cohort. Methods: 153 patients with available baseline LIPI were included. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The impact of the baseline LIPI on survival (PFS and OS), and DCR and ORR was assessed by Cox and logistic regression models respectively, adjusted for age, sex, ECOG-PS, smoking status, histology, TNM stage at diagnosis, presence of brain metastases and number of prior regimens. All p values were 2-sided, and those less than 0.05 were considered statistically significant. Results: 50.3% (n = 77) of the patients had a good (0 factors) LIPI, while 41.2% (n = 63) and 8.5% (n = 13) had intermediate (1 factor) and poor (2 factors) LIPI respectively. No significant differences were observed between the LIPI groups according to clinicopathologic characteristics. A high LIPI was significantly associated with poor OS in univariate (HR = 3.12, 95% CI 2.12 – 4.60; p < 0.0001) and multivariate (HR = 3.10, 95% CI 2.09 – 4.58; p < 0.0001) analyses. A high LIPI was associated with poor PFS (HR = 1.49, 95% CI 1.07 – 2.07; p = 0.02), but this correlation did not reach a statistical significance in multivariate analysis (HR = 1.37, 95% CI 0.98 – 1.92; p = 0.07). A higher LIPI was associated with a lower disease control rate in univariate (OR = 0.50, 95% CI 0.29 – 0.85; p = 0.01) and multivariate (OR = 0.55, 95% CI 0.31 – 0.98; p = 0.04) analyses. Conclusions: This study confirms the utility of the LIPI in prognostication and disease control prediction in advanced NSCLC patients treated with nivolumab in the second line of therapy or beyond.

Once metastatic bladder cancer has progressed to first-line treatment, the number of therapeutic options is scarce. Among chemotherapeutic agents showing activity in phase II trials, including taxanes, vinflunine (VFL) is the only one shown to increase overall survival in a phase III trial. In addition to its efficacy, VFL is safe in special population groups. Despite this, the prognosis for these patients remains poor, and more effective therapies need to be developed. Agents acting on new therapeutic targets as well as biomarkers to aid matching patients to specific treatments are currently under evaluation. In this regard, immunotherapy is showing promising results. In this article, a critical review of current treatments and future prospects is made, and therapy recommendations are made based on existing scientific evidence.

Identification of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements is a standard diagnostic test in patients with advanced non-small cell lung cancer (NSCLC). The current study describes the experience of ALK rearrangement detection of a referral center in the public health care system of Galicia in North-Western Spain. The fluorescence in situ hybridization (FISH) patterns of the ALK gene and the clinical and pathological features of these patients are reported. This study is also of interest for comparative purposes due to the relative geographical isolation of the area, which could have contributed to particular genetic features. A total of 2,045 tissue samples from NSCLC patients were collected between October 2010 and July 2015 and tested for ALK rearrangements by FISH. Examination of 1,686 paraffin-embedded tissue specimens and 395 cytological samples (306 cell block preparations and 53 cytological smears) was conducted, and any associations between the FISH results and clinicopathological features were assessed. The rate of successful evaluation was marginally higher in tissue samples than in cytological samples (92.9% vs. 84.1%); this difference was not significant. ALK rearrangements were identified in 82 patients(4%): 65 (79.3%) in tissue specimens, 15 (18.3%) in cell block samples and 2 (2.4%) in cytological smears. This genetic translocation appeared to be associated with a non-smoking history, younger age, female gender, stage IV and adenocarcinoma histological type. The findings demonstrate that ALK evaluation by FISH is feasible in tissue and cytological samples. The clinical and pathological features of the ALK-positive series of patients are similar to those previously reported in the literature.

Review [Abstract] Radionuclides have been widely used for cancer treatment. Recently, new research about radium-223 dichloride has been conducted in prostate cancer, which reveals that it is the first radiopharmaceutical to demonstrate an improvement in overall survival and time to first symptomatic skeletal event in patients with castration resistant prostate cancer with symptomatic bone metastases. This fact has created a new paradigm in the treatment of prostate cancer landscape, where only chemotherapy and hormone therapy had a role, while β-emitters had been confined exclusively to the role of pain relief with no impact on survival. The aim of this review is to outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 dichloride, reviewing patients' profile that make them suitable to therapy and chances for further studies.

[Abstract] Enzalutamide (MDV3100), an androgen receptor-signalling inhibitor, represents the most recent compound added to the therapeutic armamentarium for the treatment of metastatic castration-resistant prostate cancer (mCRPC) who progressed to docetaxel. The anti-tumour activity and safety of enzalutamide has been demonstrated in a phase III clinical trial, showing a benefit in overall survival, which was the primary endpoint. There are no head-to-head studies comparing the different treatment options in this subset of patients. In this article, most relevant data published in the literature have been reviewed, with special attention to the therapeutic alternatives currently available for postdocexatel mCRPC patients, emphasising the mechanisms of action of the different drugs, efficacy and quality of life-related aspects.

Purpose: To determine the effectiveness of a gemcitabine/cisplatin/vinorelbine combination in patients with stage III non-smallcell lung cancer (NSCLC). Patients and methods: Patients (n/46) with stage III NSCLC and naive of therapy were recruited into the trial to receive gemcitabine (G, 1000 mg/m 2 ) on days 1 and 8, cisplatin (C, 100 mg/m 2 ) on day 1 and vinorelbine (V, 25 mg/m 2 )o n days 1 and 8 every 21 days for three cycles. Results: Two patients achieved complete response (CR) and 23 partial response (PR), overall response 52%. Subsequent radical surgery included nine patients of whom four were non-resectable and five were resected and with 1 CR. Radiotherapy was administered to 31 patients, and two achieved CR. The median time to progression and overall survival were 37 and 50 weeks, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 35% of cycles, with two toxic deaths. Severe non-haematological toxicity was uncommon. Conclusions: This GCV combination is effective in patients with stage III NSCLC, and with an acceptable toxicity. # 2003 Elsevier Science Ireland Ltd. All rights reserved.

BACKGROUND The objective of this multicenter, open-labeled, Phase II study performed in Spain was to assess the efficacy and safety of irinotecan (CPT-11) as first-line chemotherapy for patients suffering from advanced colorectal carcinoma (CRC). METHODS Patients with histologically proven CRC and at least one bidimensionally measurable lesion, ages 18–70 years, with a performance status ≤ 2, normal analytical values, and no prior chemotherapy or only adjuvant chemotherapy completed before study entry were selected. The treatment schedule was CPT-11 350 mg/m2 intravenously administered once every 3 weeks. Both tumor response and toxicity were assessed using the World Health Organization and National Cancer Institute common toxicity criteria. Changes in performance status, weight, and symptoms also were measured. RESULTS Sixty-five patients (44 chemotherapy-naive patients and 21 patients who completed prior adjuvant treatment) were enrolled. Of these, 24.7% of patients responded to the treatment, and 41.5% of patients had stable disease. Patients who had not received prior adjuvant chemotherapy had a lower rate of progression on therapy (27.3%) compared with those who had received prior adjuvant chemotherapy (42.9%). The median survival was 19.9 months (range, 0.3–29.3 months). No significant differences were found in the median survival between chemotherapy-naive patients and patients who had received previous chemotherapy. Grade 3–4 diarrhea and neutropenia were the most frequent severe toxic events, which were observed in 23.1% and 30.8% of patients and in 5.9% and 10.9% of the cycles, respectively. CONCLUSIONS The current antitumor efficacy results show that 350 mg/m2 of CPT-11 administered every 3 weeks is an active and feasible first-line chemotherapy regimen for patients with CRC. Finally, the overall safety data confirmed that CPT-11 is a well tolerated treatment. Cancer 2001;91:704–11. © 2001 American Cancer Society.