First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Electronic health records and patient registries in medical oncology departments in Spain.

PURPOSE: We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain. METHODS: This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM. RESULTS: We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department. CONCLUSION: Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes. CLINICAL TRIAL REGISTRATION: Not applicable.

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL.

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study.

BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).

Preventive treatments for breast cancer: recent developments.

Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study.

BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.

Biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer.

PURPOSE: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new strategies to better use currently available agents. To assess the efficacy and safety of a biweekly regimen of cisplatin, gemcitabine and vinorelbine for advanced non-small-cell lung cancer. METHODS: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0-2 and normal organ function were eligible. Treatment consisted of cisplatin 100 mg/m(2) on day 1 plus gemcitabine, 1,000 mg/m(2) and vinorelbine 25 mg/m(2) on days 1 and 15 every 28 days. RESULTS: Of the 40 patients enrolled and assessable for response, there were five (12.5%) with confirmed complete response and 14 (35%) with a confirmed partial response for an overall response rate of 47.5%. Nine patients had stable disease while 12 (30%) progressed. Median progression-free survival and overall survival for all patients were 6.3 and 11.1 months, respectively. Toxicity was principally hematologic, with grade 3-4 neutropenia in 30%, and grade 3-4 nausea/vomiting in 22.5%. There were no treatment-related deaths. CONCLUSIONS: The biweekly regimen of cisplatin, gemcitabine and vinorelbine is associated with a high rate of response, lesser toxicity than other three-drug regimens and no benefit of survival. Therefore, the regimen under study may be an appealing alternative when considering other treatment modalities for advanced lung cancer, such as neoadjuvant therapy.

Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin-gemcitabine-vinorelbine. A phase II study.

OBJECTIVES: New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. PATIENTS AND METHODS: Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. RESULTS: Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). CONCLUSION: Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study.

Treatment of metastatic malignant melanoma with cisplatin plus tamoxifen.

A phase II study was performed to assess the efficacy and toxicity of the combination of cisplatin (CDDP) and tamoxifen (TAM) in patients with metastatic malignant melanoma (MM). A total of 31 consecutive previously untreated patients with unresectable measurable MM were given 100 mg/m2 CDDP every 21 days and 60 mg TAM every 12 h daily. All courses were given on an outpatient basis. A total of 119 courses of treatment were given. In all, 5 of the 31 patients (16%) had an objective response (95% confidence interval 5.3-34%) and 2 (6%) achieved a clinical complete response. The median duration of response was 7 months. The main side effect was gastrointestinal: 13% of the patients experienced grade 3/4 nausea/vomiting. Hematological or neurological toxicities were mild and rare. In conclusion, the combination CDDP-TAM has limited activity in MM, although its toxicity is tolerable. Our results do not allow us to recommend its use for the treatment of MM.

[Comparative study of the survival of gastric B-cell lymphoma of mucosal origin with respect to lymph node lymphoma of similar histology]. / Estudio comparativo de la supervivencia de linfomas B gástricos de origen en mucosas respecto a linfomas ganglionares de histología similar.

BACKGROUND: The differences in clinical presentation, morphology, phenotype and genetic changes between lymphomas originating in the gastrointestinal tract and the lymph nodes justified the proposal of a system of specific classification for lymphomas originating in lymphoid tissue associated to mucosa (MALT). Nevertheless, there is no conclusive evidence that the types of lymphoma defined as such have a different clinical evolution with respect to the lymph nodes lymphomas. METHODS: With the aim of analyzing this problem a clinical follow up of 33 patients with primary gastric lymphomas (high and low grade) was compared with the results of a group of 99 lymphomas of the lymph nodes was carried out with classification according to the criteria of Kiel classification and the proposal by Isaacson et al for MALT lymphomas. Survival obtained by the Kaplan-Meier method was compared by the Mantel-Haenzel test. RESULTS: The results obtained showed that all gastric lymphomas have a less aggressive evolution than those of lymph node origin (p < 0.01). This significant statistical difference was also observed when lymphomas of similar histology were compared. Similarly, the subgroups of large cell lymphoma (p < 0.05) and small cells (p < 0.01) differ with respect to lymphomas of similar histology and of lymph node origin. In contrast with the results expected, no significant difference was observed between the two main groups of lymphomas of high and low grade mucosal origin. CONCLUSIONS: The analysis of the results supports the convenience of a system of specific classification for lymphomas of mucosal origin. Nevertheless, the specific existence of groups of high and low grade lymphomas is questioned since the probability of survival between both subgroups does not show statistically significant differences.

Non-small-cell lung cancer (NSCLC): chemotherapy in advanced disease. Our experience in ten years.

This is a review of the therapeutic schedules used in our service during the past 10 years for the therapy of advanced non-small-cell lung cancer. During the first years, nonrandomized trials were conducted and several combinations were tested: MACC (methotrexate, doxorubicin, cyclophosphamide, and CCNU), cisplatin-etoposide, and cisplatin-vindesine. The results of these trials were invariably discouraging: objective responses hardly reached 30%, while the survival was around 15 months in the best case. On December 1985 a new randomized trial, based on the combination MIP (mytomicin, ifosfamide, cisplatin) was designed; 60.7% of objective responses were achieved, with 9 complete remissions (17.6%) and 22 partial remissions (43.1%). Median survival was 15 months. In order to reduce the toxicity of this combination, carboplatin was substituted for cisplatin. Unfortunately, results were very poor. No complete remission, and only 5 partial responses (20%) were achieved. At the present time, a new randomized trial is being conducted. In it, MIP combination is compared with VIP (vindesine, ifosfamide, cisplatin). Preliminary results have shown no differences between both arms in response, toxicity, or survival. New therapeutic approaches, as neoadjuvant therapy, are being explored.

Antiemetic regimens in outpatients receiving cisplatin and non-cisplatin chemotherapy. A randomized trial comparing high-dose metoclopramide plus methylprednisolone with and without lorazepam.

Results of a randomized trial on antiemesis for cisplatin (CDDP) and non-CDDP chemotherapy-induced vomiting are reported. One hundred and sixty-three outpatients received 282 chemotherapy courses (141 with CDDP and 141 without CDDP). Patients were randomly assigned to receive either high-dose metoclopramide plus methylprednisolone (arm A) or the same drugs plus lorazepam (arm B). In both arms a high protection rate for vomiting was obtained, on the whole without statistically significant differences. Patients who received lorazepam had, however, significantly fewer nausea episodes during first day post-chemotherapy (p less than 0.05). Arm B was also superior in anxiety control during the first day of chemotherapy (p less than 0.01). Both regimens were significantly more effective in patients who had not been given chemotherapy previously (p less than 0.01). No differences in antiemetic protection were found between CDDP and non-CDDP courses. No significant differences were found in premonitory vomiting control between the two arms of the trial. Toxicity was very mild with both regimens, although sedation was significantly higher in arm B (p less than 0.001). We conclude that high-dose metoclopramide plus methylprednisolone is a highly effective combination for chemotherapy-induced nausea and vomiting, and that it is quite suitable for outpatient use. Lorazepam did not significantly increase the antiemetic potency of the combination, nor did it improve premonitory vomiting control, although it gave a better control of acute nausea and anxiety.