Pembrolizumab with or Without Lenvatinib as First-line Therapy for Patients with Advanced Urothelial Carcinoma (LEAP-011): A Phase 3, Randomized, Double-Blind Trial.

BACKGROUND: Pembrolizumab plus lenvatinib has shown antitumor activity and acceptable safety in patients with platinum-refractory urothelial carcinoma (UC). OBJECTIVE: To evaluate pembrolizumab plus either lenvatinib or placebo as first-line therapy for advanced UC in the phase 3 LEAP-011 study. DESIGN, SETTING, AND PARTICIPANTS: Patients with advanced UC who were ineligible for cisplatin-based therapy or any platinum-based chemotherapy were enrolled. INTERVENTION: Patients were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 wk plus either lenvatinib 20 mg or placebo orally once daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dual primary endpoints were progression-free survival (PFS) and overall survival (OS). An external data monitoring committee (DMC) regularly reviewed safety and efficacy data every 3 mo. RESULTS AND LIMITATIONS: Between June 25, 2019 and July 21, 2021, 487 patients were allocated to receive lenvatinib plus pembrolizumab (n = 245) or placebo plus pembrolizumab (n = 242). The median time from randomization to the data cutoff date (July 26, 2021) was 12.8 mo (interquartile range, 6.9-19.3). The median PFS was 4.5 mo in the combination arm and 4.0 mo in the pembrolizumab arm (hazard ratio [HR] 0.90 [95% confidence interval {CI} 0.72-1.14]). The median OS was 11.8 mo for the combination arm and 12.9 mo for the pembrolizumab arm (HR 1.14 [95% CI 0.87-1.48]). Grade 3-5 adverse events attributed to trial treatment occurred in 123 of 241 patients (51%) treated with lenvatinib plus pembrolizumab and in 66 of 242 patients (27%) treated with placebo plus pembrolizumab. This trial was terminated earlier than initially planned based on recommendation from the DMC. CONCLUSIONS: The benefit-to-risk ratio for first-line lenvatinib plus pembrolizumab was not considered favorable versus pembrolizumab plus placebo as first-line therapy in patients with advanced UC. PATIENT SUMMARY: Lenvatinib plus pembrolizumab was not more effective than pembrolizumab plus placebo in patients with advanced urothelial carcinoma.

Which biological pathways are responsible for the late appearance of brain metastases in renal cell carcinoma? Analysis of eight cases.

Background: Renal cell carcinoma (RCC) represents 1% of all cancers and its brain metastases amount to 8.1% of all metastatic tumors. Late brain metastases are defined as tumors that appear 10 years after diagnosis of the primary lesion. The objective of this work is to discuss which biological pathways are responsible for the late appearance of these metastases analyzing eight cases. Case Description: We report here eight cases of late brain metastases of RCC treated between 2018 and 2021. Patients consulted for different clinical complaints. Brain magnetic resonance imaging and computed tomography scan were performed on all patients. They were treated by complete surgical resection plus radiosurgery or by radiosurgery alone. The histology of most metastases showed clear cell RCC. Conclusion: In the presence of a patient with an intracranial tumor and a history of RCC with more than 10 years of evolution, the presence of late metastasis should always be considered. There are many theories described in the literature that try to explain the late appearance of brain metastases from RCC (low mitotic index, impaired immune system, cross talk, self-seeding, and among others).

Patterns of Disease Progression and Outcome of Patients With Testicular Seminoma Who Relapse After Adjuvant or Curative Radiation Therapy.

PURPOSE: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy. METHODS AND MATERIALS: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse. RESULTS: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression. CONCLUSIONS: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy.

Access of patients with breast and lung cancer to chemotherapy treatment in public and private hospitals in the city of Buenos Aires.

OBJECTIVES: Describe the time elapsed from the diagnosis to treatment with chemotherapy for patients with breast and lung cancer at public and private hospitals in Buenos Aires. DESIGN: Retrospective cohort study. SETTING: Three public and three private academic hospitals in Buenos Aires. PARTICIPANTS: Patients with breast (n = 168) or lung cancer (n = 100) diagnosis treated with chemotherapy. MAIN OUTCOMES MEASURES: Clinical and sociodemographic data were collected in a stratified sample. We used the Kaplan-Meier estimator to analyse the time elapsed and the log rank test to compare both groups. RESULTS: For breast cancer patients, median time elapsed between diagnosis and treatment with chemotherapy was 76 days (95% CI: 64-86) in public and 60 days (95% CI: 52-65) in private hospitals (P = 0.0001). For adjuvant and neoadjuvant treatments, median time was 130 (95% CI: 109-159) versus 64 (95% CI: 56-73) days (P < 0.0001) and 57 days (95% CI: 49-75) versus 26 (95% CI: 16-41) days, respectively (P = 0.0002). There were no significant differences in the time from first consultation to diagnosis. In patients with lung cancer, median time from diagnosis to treatment was 71 days (95% CI: 60-83) in public hospitals and 31 days (95% CI: 24-39) in private hospitals (P = 0.0002). In the metastatic setting, median time to treatment was 63 days (95% CI: 45-83) in public and 33 (95% CI: 26-44) days in private hospitals (P = 0.005). CONCLUSIONS: There are significant disparity in the access to treatment with chemotherapy for patients in Buenos Aires, Argentina.

Transformación de teratoma en rabdomiosarcoma / Transformation of teratoma in rabdomiosarcoma

Los teratomas son tumores germinales malignos compuestos por dos o más capas de tejido, que ocasionalmente se transforman en estirpes con crecimiento agresivo. Se presenta el caso de un paciente de 29 años con un tumor germinal gonadal localizado en testículo, cuya evolución fue desfavorable por presentar transformación en un fenotipo correspondiente a un rabdomiosarcoma. La patología aquí descripta deviene del crecimiento diferencial de un componente ya existente en el tumor original o la transformación en un linaje somático que se hace dominante. Los tumores transformados como el del caso descripto son raros y presentan características diferentes de la mayoría de las neoplasias germinales respecto del comportamiento, el pronóstico y la sensibilidad a los tratamientos establecidos.

Teratomas are malign germ cell tumors composed of two or more tissue layers. When there is specific organ differentiation they are called mature teratoma. They rarely grow aggressively. We report the case of a 29 year-old man with a diagnosis of gonadal germ cell tumor whose evolution was unfavorable owing to transformation into a different phenotype corresponding to a rhabdomyosarcoma. This phenomenon occurs through differential growth of a single histological component of the original tumor or transformation of a somatic lineage that becomes dominant. Transformed tumors such as the one herein described differ from most germ cell neoplasms regarding behavior, prognosis, and susceptibility to established treatments.