Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status (PS) are underrepresented in clinical trials. We evaluate the efficacy and safety of ICIs in a real-world setting. METHODS: We conducted a multi-institutional retrospective study to assess clinical outcomes of NSCLC treated with ICIs. We categorized pts within two groups (PS 0-1 vs 2) and assessed clinical outcomes and safety. RESULTS: Two hundred and sixty nine patients were included, 44 patients (16.4%) had baseline PS 2 and 223 patients (82.9%) PS 0-1. The overall response rate (ORR) was 30.4%, median PFS was 7.26 months (95% CI 5.1-9.4), and median OS was 15.18 months (95% CI 9.5-20.9). Patients with a PS 2 were most likely to received ICIs in the second or later line (84.1% vs 64.6%; p = 0.01), had baseline steroids (21.4% vs 8.2%; p 0.010), lower response rate (16.7% vs 34.5%; p 0.02) and clinical benefit (35.7% vs 71%; p 0.000) compared to PS 0-1 pts. Moreover, PS ≥ 2 patients had shorter PFS, median 2.2 months (95% CI 1.3-3.1) compared to 9.9 months (95% CI 6.7-13.1] and shorter OS, 3.3 months (95% CI 2.6-4.2) versus 24.1 months (95% CI 16.1-32.1), respectively. PS was significantly associated with PFS and OS in multivariate analysis. As it was expected, immunotherapy was well tolerated with a safety profile comparable to the previous published data. CONCLUSION: Based on these retrospective results, patients with poor baseline performance status seem to have poor clinical outcomes with ICIs in the real-world setting.

Peripheral changes in immune cell populations and soluble mediators after anti-PD-1 therapy in non-small cell lung cancer and renal cell carcinoma patients.

Patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) have shown benefit from anti-PD-1 therapies. However, not all patients experience tumor shrinkage, durable responses or prolonged survival, demonstrating the need to find response markers. In blood samples from NSCLC and RCC patients obtained before and after anti-PD-1 treatment, we studied leukocytes by complete blood cell count, lymphocyte subsets using flow cytometry and plasma concentration of nine soluble mediators, in order to find predictive biomarkers of response and to study changes produced after anti-PD-1 therapy. In baseline samples, discriminant analysis revealed a combination of four variables that helped differentiate stable disease-response (SD-R) from progressive disease (PD) patients: augmented frequency of central memory CD4+ T cells and leukocyte count was associated with response while increased percentage of PD-L1+ natural killer cells and naïve CD4+ T cells was associated with lack of response. After therapy, differential changes between responders and non-responders were found in leukocytes, T cells and TIM-3+ T cells. Patients with progressive disease showed an increase in the frequency of TIM-3 expressing CD4+ and CD8+ T cells, whereas SD-R patients showed a decrease in these subsets. Our findings indicate that a combination of immune variables from peripheral blood (PB) could be useful to distinguish response groups in NSCLC and RCC patients treated with anti-PD-1 therapy. Frequency of TIM-3+ T cells showed differential changes after treatment in PD vs SD-R patients, suggesting that it may be an interesting marker for monitoring progression during therapy.

[Aggresive angiomyxoma after renal transplantation]. / Angiomixoma agresivo postrasplante renal.

The condition of immunosuppressed increases the risk of cancer in kidney transplant patients, as compared to the general population. The best survival of inmunosupressed patients in recent years has turned both neoplasms and cardiovascular diseases into the main causes of morbidity and mortality. We present the case of a renal transplanted patient who developed an unusual form of mesenchymal tumor such as the aggressive angiomyxoma, four years after the implant and requiring wide surgical resection.

First-line cisplatin, docetaxel, and cetuximab for patients with recurrent or metastatic head and neck cancer: A multicenter cohort study.

BACKGROUND: The targeted therapy cetuximab [directed at the epidermal growth factor receptor (EGFR)] in combination with 5-fluorouracil and platinum-based chemotherapy (the EXTREME regimen) has shown substantial efficacy for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Thus, this scheme has been established as the preferred first-line option for these patients. However, more recently, a new strategy combining platinum, taxanes, and cetuximab (the TPEx regimen) has demonstrated similar efficacy with a more favorable toxicity profile in clinical trials. AIM: To evaluate the safety and efficacy of the TPEx scheme as first-line therapy in advanced SCCHN in a multicenter cohort study. METHODS: This retrospective multicenter cohort study included patients with histologically confirmed recurrent or metastatic SCCHN treated with first-line TPEx at five medical centers in Argentina between January 1, 2017 and April 31, 2020. Chemotherapy consisted of four cycles of docetaxel, cisplatin, and cetuximab followed by cetuximab maintenance therapy. Clinical outcomes and toxicity profiles were collected from medical charts. Treatment response was assessed by the investigator in accordance with Response Evaluation Criteria in Solid Tumors (version 1.1). Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Twenty-four patients were included. The median age at diagnosis was 58 years (range: 36-77 years). The majority of patients (83.3%) received at least four chemotherapy cycles in the initial phase. In the included group, the overall response rate was 62.5%, and 3 patients achieved a complete response (12.5%). The median time to response was 2.4 mo [95% confidence interval (CI): 1.3-3.5]. With a median follow-up of 12.7 mo (95%CI: 8.8-16.6), the median progression-free survival (PFS) was 6.9 mo (95%CI: 6.5-7.3), and the overall survival rate at 12 mo was 82.4%. Patients with documented tumor response showed a better PFS than those with disease stabilization or progression [8.5 mo (95%CI: 5.5-11.5) and 4.5 mo (95%CI: 2.5-6.6), respectively; P = 0.042]. Regarding the safety analysis, two-thirds of patients reported at least one treatment-related adverse event, and 25% presented grade 3 toxicities. Of note, no patient experienced grade 4 adverse events. CONCLUSION: TPEx was an adequately tolerated regimen in our population, with low incidence of grade 3-4 adverse events. The median PFS were consistent with those in recent reports of clinical trials evaluating this treatment combination. This regimen may be considered an attractive therapeutic strategy due to its simplified administration, decreased total number of chemotherapy cycles, and treatment tolerability.

Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years?

Thoracic radiotherapy (TRT) is one of the main treatments in limited-stage small cell lung cancer (LS-SCLC). Hyperfractionated TRT (45 Gy, 1.5 Gy twice daily) has been the standard of care (SOC) since Turrisi and colleagues published the results of their clinical trial in 1999. Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival (OS). The phase 2 trial by Grønberg et al (2016) comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate, progression-free survival (PFS), grade 3-4 adverse effects, and OS. The CONVERT trial, published in 2017, failed to demonstrate the superiority of the conventional scheme (once-daily TRT) vs twice-daily radiotherapy, despite the application of modern radiotherapy techniques and a quality assurance programme, thus confirming the twice-daily hyperfractionated regimen as the SOC. At the 2020 American Society of Clinical Oncology (ASCO) annual meeting, Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens (45 Gy vs 60 Gy), both administered twice daily. Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm (70.2% vs 46.1%, P = 0.002), despite similar objective response rates and PFS outcomes. Those findings provide a new treatment alternative to consider: Hyperfractionated, high-dose TRT. However, the results of that trial will need to be validated in a large, randomized phase 3 study. The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen. The potential role of upfront immunotherapy, which early data suggest may improve OS, also needs to be determined.

Angiomixoma agresivo postrasplante renal / Aggresive angiomyxoma after renal transplantation

La condición de inmunosuprimido aumenta el riesgo de cáncer en trasplantados renales, en comparación a la población general. La mejor supervivencia de esta población en los últimos años ha convertido a las neoplasias y a la enfermedad cardiovascular en las principales causas de morbi-mortalidad. Presentamos el caso de un paciente trasplantado renal que desarrolló cuatro años después del trasplante una forma inusual de tumor mesenquimatoso, el angiomixoma agresivo, que requirió resección quirúrgica amplia.

The condition of immunosuppressed increases the risk of cancer in kidney transplant patients, as compared to the general population. The best survival of inmunosupressed patients in recent years has turned both neoplasms and cardiovascular diseases into the main causes of morbidity and mortality. We present the case of a renal transplanted patient who developed an unusual form of mesenchymal tumor such as the aggressive angiomyxoma, four years after the implant and requiring wide surgical resection.