Breast sarcomas are rare mesenchymal-derived breast tumors. The small number of patients, the different histological subtypes, and the variation in clinical practice impairs the ability to draw firm ...practice recommendations. Patient management is often extrapolated from other soft tissue sarcomas, mostly of the extremities in which more clinical data is available. Surgical resection with negative margins is the goal of treatment, irrespective of the surgical procedure; the implication of radiation and chemotherapy is variable. Further advances in treatment should follow the assembly of breast sarcoma patients in specific cancer networks in specialized sarcoma referral centers. The characterization of molecular pathways active in tumorogenesis of these tumors may pave the way for the application of novel therapeutic agents.
ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world ...multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients.
Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT).
At a median follow-up of 41 months (95% confidence interval CI: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio HR 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079).
We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi.
Until recently, metastatic melanoma was a disease with limited treatment options and a poor prognosis. Dacarbazine was accepted as the standard treatment for melanoma in the 1970s, and despite ...inducing an overall survival of approximately 7.4 months, it remained so until relatively recently. In the last few years, significant advances in the molecular understanding of this disease have facilitated the development of novel and promising drugs. Precision-oriented medicine is currently revolutionizing the practice of oncology. Targeted therapies have demonstrated great potential in treating melanoma and various other types of cancer, including breast, colorectal and non-small cell lung cancer. Here, we review the evolution of melanoma treatment from single-agent chemotherapy to combination therapy, the emergence of immunotherapy in melanoma and the development of targeted therapies, such as the use of the BRAF inhibitor as a treatment agent. The ability to treat melanoma according to the fingerprint of the tumor reflects an overall change in the practice of oncology.
A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a ...retrospective chart review of participating patients.
Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation.
A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs.
The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The widespread use of immune checkpoint inhibitors (ICI) has become a mainstay of care for a variety of malignancies. However, these therapies portend a range of adverse effects, including a ...potentially fatal form of cardiotoxicity which to date has not been elucidated. We aimed to evaluate the baseline characteristics of ICI-mediated cardiotoxicity. We performed a retrospective study evaluating patients treated with ICI who performed at least 2 echocardiography examinations, before and after the initiation of ICI. Cardiotoxicity was defined as Cancer Therapeutics-related Cardiac Dysfunction (CTRCD) development, with an absolute left ventricular ejection fraction reduction of >10%, to a value <53%. Fifty-two patients were included with a male preponderance (65%) and a mean age of 66 (±12) years. Twelve (23%) patients developed CTRCD, of which 2 patients were diagnosed with myocarditis. Among the CTRCD group, patients tended to be older and more likely to have baseline diastolic dysfunction: lower e' septal (P=0.026), higher E/e' septal (P=0.035), and a trend of E/e' average (P=0.076). All-cause and cardiovascular hospitalizations were significantly more common among the CTRCD group (P=0.028 and 0.001, respectively). Higher prevalence of cardiovascular mortality was observed among the CTRCD group (25% vs. 2%, P=0.034). We evaluated the development of CTRCD among patients treated with ICI therapies. Our findings suggest that baseline diastolic parameters may be associated with CTRCD development assisting in the early diagnosis of ICI-induced cardiac injury.
Objective
Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are ...exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX).
Patients and methods
Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression-free survival (PFS), adverse events, and other relevant clinical data were analyzed.
Results
The median patients’ age was 49 (range 28–68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3–30.3). No significant adverse events were observed.
Conclusions
Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.
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