Pathological complete response induced by first-line chemotherapy with single agent docetaxel in a patient with advanced non small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Defining the optimal treatment for patients with inoperable non small cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer a chance for these patients for radical surgical resection and, possibly, complete recovery.</p> <p>Case Presentation</p> <p>A 62-year old man with IIIA-N2 inoperable NSCLC was treated with first-line single agent docetaxel. A platinum-based treatment, though considered more active, was ruled out because of renal impairment. The patient tolerated the treatment very well and, although his initial response was not impressive, after 14 cycles he obtained a complete clinical response, which was confirmed pathologically after he underwent surgical lobectomy.</p> <p>Conclusion</p> <p>In non-operable NSCLC patients not eligible for a platinum-based treatment, single-agent docetaxel can provide complete pathologic responses. Failure to obtain a response after the first few cycles should not automatically discourage to continue treatment.</p

Early primary tumor response in metastatic RCC patients treated with immune checkpoint inhibitors-based combinations

Background: 25-30% of renal cell carcinoma presents with metastases (mRCC) at diagnosis. The activity of immune checkpoint inhibitor (ICI)-combinations on the primary tumor (PT) is debated. Patients andMethods: mRCC patients (pts) with PT who received first-line nivolumab plus ipilimumab (N/I) or pembrolizumab plus axitinib (P/A) were included. We investigated the early primary tumor response (EPTR) at the first radiological assessment. Results: 73 pts were included. The median early reduction of the PT longest diameter was 12.4% with P/A versus 6.2% with N/I (p = 0.42). We evaluated if the type of EPTR could affect the metastases response. Among pts with PT stable disease (SD), 8.3% had metastatic disease progression (PD) with P/A and 34.8% with N/I. Early PT partial response (PR) was associated with no metastatic PD with both N/I and P/A. The 2 pts with PT PD had also metastatic PD to P/A. Of the 3 PT with PD to N/I, 1 had metastatic SD and 2 PD. In the overall population, of the 94.1% without PT progression (PR+SD), 47.5% had metastatic PR, 35.6% SD, 16.9% PD. Conclusions: ICIs-combinations achieved an early PT PR in about 10-20%, without any complete responses. Only a small percentage of PT had an early PD, mainly associated with metastatic PD. However, among those PT without an early progression, metastatic PR can be achieved in approximately 50% of cases

Role of FGFR3 in bladder cancer: Treatment landscape and future challenges

: Bladder cancer is a heterogeneous malignancy and is responsible for approximately 3.2% of new diagnoses of cancer per year (Sung et al., 2021). Fibroblast Growth Factor Receptors (FGFRs) have recently emerged as a novel therapeutic target in cancer. In particular, FGFR3 genomic alterations are potent oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR inhibitors. Indeed, overall ∼50% of bladder cancers have somatic mutations in the FGFR3 -coding sequence (Cappellen et al., 1999; Turner and Grose, 2010). FGFR3 gene rearrangements are typical alterations in bladder cancer (Nelson et al., 2016; Parker et al., 2014). In this review, we summarize the most relevant evidence on the role of FGFR3 and the state-of-art of anti-FGFR3 treatment in bladder cancer. Furthermore, we interrogated the AACR Project GENIE to investigate clinical and molecular features of FGFR3-altered bladder cancers. We found that FGFR3 rearrangements and missense mutations were associated with a lower fraction of mutated genome, compared to the FGFR3 wild-type tumors, as also observed in other oncogene-addicted cancers. Moreover, we observed that FGFR3 genomic alterations are mutually exclusive with other genomic aberrations of canonical bladder cancer oncogenes, such as TP53 and RB1. Finally, we provide an overview of the treatment landscape of FGFR3-altered bladder cancer, discussing future perspectives for the management of this disease

Sequential Treatment with Pazopanib and Everolimus in Metastatic Renal Cell Carcinoma

In metastatic renal cell carcinoma, complete response to first-line antiangiogenic agents is rare and resistance to therapy often develops. Protocols for sequential treatment with angiogenesis and mTOR inhibitors are under evaluation to improve outcomes. In this observational, real-world study, patients received a first-line therapy with pazopanib until discontinuation for disease progression or toxicity, then a second-line with everolimus. Primary endpoints were overall survival (OS) for sequence, progression free survival (PFS) for each agent, and safety. Thirty-one patients were included in the analysis: 73.3% of patients underwent nephrectomy before treatment, 25.8% had at least three comorbidities. At the beginning of therapy, the median age was 68 years, with more than 60% of patients older than 65 years. The median OS for sequence was 26.5 months (95% CI 17.4-nc); median PFS was 10.6 months (95% CI 6.3–12.1) with pazopanib and 5.3 months (95% CI 3.8–6.7) with everolimus. The median persistence in pazopanib therapy was 8.1 months (Interquartile Range IQR 5.3–12.7), with 31% of patients who required dose reduction, while persistence in everolimus was 4.4 months (IQR 3.4–6.5). Sequence was well tolerated with a different profile of adverse events for each agent. These data confirmed that pazopanib was effective, even in reduced dosing, and well tolerated and suggested that everolimus may represent an opportunity to continue a therapy when patients cannot further tolerate angiogenesis inhibitors or develop a resistance

Statin Use and Survival in Patients with Metastatic Castration-resistant Prostate Cancer Treated with Abiraterone Acetate

Background: Although statin use has been associated with favorable effects in various solid malignancies, no conclusive evidence is available at present. Statins are safe and inexpensive, and may synergize with novel antiandrogen agents abiraterone via pharmacokinetic interactions and decrease substrate availability for de novo androgen biosynthesis. Objective: To determine whether statin use affects survival in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone. Design, setting, and participants: Medical records of patients with documented mCRPC between September 2011 and August 2016 were reviewed at multiple participating centers. This research was conducted in ten institutions, including both referral centers and local hospitals. A total of 187 patients receiving abiraterone for mCRPC between September 2011 and August 2016 were eligible for inclusion in this retrospective study. Outcome measurements and statistical analysis: Patients were assessed for overall survival (OS), statin use at the time of treatment initiation, prostate-specific antigen (PSA) variations, and other variables of interest. Univariable and multivariable analysis was used to explore the association of variables of interest with OS and PSA declines. Results and limitations: Statin use was a significant prognostic factor for longer OS in univariable (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.37-0.72; p 50% decline at 12 wk: 72.1% in statin users vs 38.5% in non-users; p <. 0.001). Conclusions: Our study suggests a prognostic impact of statin use in patients receiving abiraterone for mCRPC. The mechanism of this interaction warrants elucidation, but may include enhancement of the antitumor activity of abiraterone as well as cardioprotective effects. Patient summary: We assessed the effects of statin use in patients with advanced prostate cancer receiving abiraterone. Patients treated with a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further studies assessing the use of abiraterone plus statins are warranted. Patients with advanced prostate cancer receiving a statin plus abiraterone appeared to live longer than those treated with abiraterone only. Since no negative drug-drug interaction is known and statins are widely used and inexpensive, further prospective studies are warranted

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors

Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. Methods: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. Results: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). Conclusions: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments

PSA declines and survival in patients with metastatic castration-resistant prostate cancer treated with enzalutamide: A retrospective case-report study

Rationale: PSA responses have been associated with a survival benefit in patients treated with enzalutamide in retrospective analyses. Patient concerns: However the prognostic value of PSA declines in highly pretreated patients receiving enzalutamide remains to be defined. Diagnoses and interventations: Medical records of patients with documented mCRPC treated with enzalutamide between September 2011 and August 2016 were reviewed at multiple participating centers and assessed for overall survival (OS), PSA variations, and other variables of interest. Univariable and multivariable analyses were conducted. Outcomes: A total of 129 patients received enzalutamide. PSA response rates (>50% PSA declines) were 58/119 (48.7%), 58/115 (50.4%), 54/110 (49.1%), and 47/91 (51.7%) at weeks 4, 8, 12, and 16, respectively. Having a PSA response was a statistically significant prognostic factor of improved OS at 8 and 12 weeks in univariable analysis, whereas it was significant at 12 weeks in the multivariable analysis. Patients treated with enzalutamide had a median OS of 7.8 months. Lessons: Our study supports the prognostic value of PSA declines in heavily treated patients receiving enzalutamide

The Third Law of Thermodynamics Course in Theoretical Physics Teaching Universities

Рассматривается методика изложения темы «третий закон термодинамики».Methodology of exposition of theme is examined the «third law of thermodynamics»