Abstract Objectives To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who ...continue at the standard dose. Patients and methods All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. Results A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42–2.29; P <0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy ( P = 0.007). Conclusions Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Targeted therapies have improved survival in patients with metastatic renal cell cancer (RCC); however, expert opinion on the optimal therapeutic strategy is divided. This retrospective study ...evaluates different sequential schemes of targeted therapies in 310 patients with advanced/metastatic RCC who received different systemic agents - sorafenib, sunitinib, bevacizumab, everolimus, temsirolimus and axitinib - alone or in different sequences, until disease progression or intolerable toxicity (median follow-up: 37 months). The median overall survival (OS) was 22 months and the 5-year OS was 23.4%; differential therapeutic schemes were not associated with differences in OS. A worse performance status, no nephrectomy and a poor-risk classification according to the Motzer criteria was associated with a shorter OS. These findings support the use of targeted therapies in the treatment of RCC, even in a large unselected population from a single institution, and suggest that treatment should be tailored to meet individual circumstances and needs.
Sarcomatoid renal cell carcinoma (sRCC) represents a rare form of renal cell carcinoma marked by an aggressive biology, poor prognosis and little benefit from anti-angiogenic targeted therapy. More ...promising results come from the recent therapeutic strategy based on immune checkpoint inhibitor (ICI) combinations.
For this meta-analysis, we searched MEDLINE/PubMed, the Cochrane Library and American Society of Medical Oncology (ASCO) Meeting abstracts for phase II or III randomised clinical trials. Data extraction was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence intervals were extracted from studies. Summary HRs were calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies.
Four studies were selected for final analysis, including 467 patients (226 treated in with ICI combinations and 241 received sunitinib in the control arms). ICI-based combinations were associated with an improved PFS and OS compared with sunitinib, with a reduction of more than 40% of progression (HR = 0.56; p < 0.0001) and mortality (HR = 0.56; p = 0.001) risk. Moreover, ICI-based combinations are associated with a objective response rate (ORR) of more than 50% (versus 20% with sunitinib), corresponding to a doubled risk of achieving an ORR compared with controls (relative risk RR = 2.15; p < 0.00001). Finally, immunotherapy significantly increased the possibility to obtain complete responses (RR = 8.15, p = 0.0002) with an incidence of 11%.
Our data support the efficacy of ICI-based combinations for sRCC therapy, redefining the first-line treatment.
•Sarcomatoid RCC (sRCC) is marked by aggressive biology and poor prognosis.•We performed a meta-analysis of the efficacy of immune checkpoint inhibitor (ICI)–based combinations for sRCC.•Four studies were selected for the final analysis, with a total of 467 patients.•ICI-based combinations improved progression-free survival, overall survival and overall response rate compared with sunitinib.•Our data support the efficacy of ICI-based combinations for sRCC first-line therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Wild type RAS ( RAS -wt) status is predictive of the activities of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab (C) and panitumumab (P). We ...examined the impact of C and P on progression-free survival (PFS), overall survival (OS) and overall response rate (ORR) in advanced colorectal cancer (CRC) patients who have RAS -wt/ BRAF- mutant ( BRAF -mut) status. Methods Randomised trials that compared C or P plus chemotherapy (or C or P monotherapy) with standard therapy or best supportive care (BSC) were included. We used published hazard ratios (HRs) if they were available, or we derived treatment estimates from other survival data. Pooled estimates of the treatment efficacy of anti-EGFR-based therapy with C or P for the RAS -wt/ BRAF -mut subgroup were calculated with the random-effect inverse variance weighted method. All statistical tests were two-sided. Results Nine phase III trials and one phase II trial (six first-line and two second-line trials, plus two trials involving chemorefractory patients), that included 463 RAS -wt /BRAF -mut CRC patients, were analysed. Overall, the addition of C or P treatment in the BRAF -mut subgroup did not significantly improve PFS (HR, 0.88; 95% confidence interval (CI), 0.67–1.14; p = 0.33), OS (HR, 0.91; 95% CI, 0.62–1.34; p = 0.63) and ORR (relative risk, 1.31; 95% CI 0.83–2.08, p = 0.25) compared with control regimens. Conclusions C- or P-based therapy did not increase the benefit of standard therapy or the BSC in RAS -wt/ BRAF -mut CRC patients. These findings support BRAF mutation assessment before initiation of treatment with anti-EGFR monoclonal antibodies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Everolimus is an oral inhibitor of mammalian target of rapamycin (mTOR-I) and is currently approved for the treatment of metastatic renal cell carcinoma (mRCC) after failure of first-line vascular ...endothelial growth factor receptor tyrosine kinase inhibitor (TKI).
In this narrative review, we aim to report the available evidence about the use of everolimus as second-line therapy for mRCC. A literature search was performed using PubMed/MEDLINE and abstracts from major conferences on clinical oncology as sources. We report data from prospective as well as retrospective and real world data studies and we analyze the safety and efficacy profile of everolimus as second-line therapy for mRCC.
Although different drugs are currently available for the second-line treatment of mRCC, everolimus represents a feasible and safe option in this setting, especially for patients who have experienced high-grade toxicity or are still carrying TKI-related toxicities from first-line treatment.
Current landscape of treatment of castration-resistant prostate cancer (CRPC) has recently changed. Cabazitaxel, a new taxane with potential antineoplastic activity, has been approved by Food and ...Drug Administration (FDA) after docetaxel failure. In a phase III trial, cabazitaxel showed increased overall survival (OS) compared with mitoxantrone (15.1 vs. 12.7 mo, HR 0.70, 95% CI 0.59-0.83, p < 0.0001). Furthermore, chemotherapy is not the only strategy available: several studies have shown as CRPC remains dependent on androgen receptor function for growth. Abiraterone acetate, an irreversible inhibitor of CYP17, has also been approved by FDA after docetaxel failure. In a phase III trial comparing abiraterone acetate to placebo, abiraterone showed improvement in OS (14.8 vs. 10.4 mo, HR 0.65, 95% CI 0.54-0.77; p < 0.0001).
This review will discuss current options and the ongoing trials for second-line treatment of CRPC including chemotherapy, hormonal therapies, antiangiogenetic and immune strategies.
The addition of either docetaxel or an androgen receptor signalling pathway inhibitor (ARSi) to androgen-deprivation therapy (ADT) has become the standard of care for metastatic castration-sensitive ...prostate cancer (mCSPC) patients. Recent phase III data support even greater survival impact of a triplet regimen with ADT plus docetaxel plus an ARSi (abiraterone or darolutamide) compared to ADT plus docetaxel.
To evaluate whether the addition of an ARSi to ADT improves outcomes of mCSPC patients treated with docetaxel.
We searched MEDLINE/PubMed, the Cochrane Library, and ASCO Meeting abstracts for randomised clinical trials (RCTs) testing the combination of ARSi + ADT in mCSPC men who received docetaxel. Data extraction was conducted according to the PRISMA statement. Summary hazard ratio (HR) was calculated using random- or fixed-effects models. The statistical analyses were performed with RevMan software (v.5.2.3).
Five RCTs were selected. Triplet therapy improved overall survival (OS) compared to ADT + docetaxel in mCSPC patients (HR = 0.73; p < 0.00001). This intensified strategy maintained the OS benefit when the ARSi was administered concomitant to chemotherapy (HR = 0.72; p < 0.00001), but no statistical effect was detected if the ARSi was sequential to docetaxel (p = 0.44). Moreover, in the subgroup of men with de novo mCSPC, triplets significantly improved OS (HR = 0.72, p < 0.0001). The lack of access to raw data was the main limit of our analysis.
Our results support a clear survival advantage of adding an ARSi to ADT in mCSPC patients treated with docetaxel, mainly when the ARSi was administered concomitantly to chemotherapy and in the subgroup of de novo mCSPC.
•Triplet (ADT + docetaxel + ARSi) improves OS compared to ADT + docetaxel in mCSPC.•The OS advantage is greater with ADT + docetaxel + ARSi administered concomitantly.•In the subgroup of de novo mCSPC the triplet significantly improves OS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Study Type – Prognosis (cohort series)
Level of Evidence 2b
What's known on the subject? and What does the study add?
In the literature, few studies have evaluated the role of tumour burden (TB) in ...metastatic real cell carcinoma (mRCC), even though it has been considered as important in localized tumours. In metastatic patients the role of TB is uncertain because it was analyzed in chemotherapy treated patients or using a partial evaluation of TB.
This study, first reports the independent prognostic and predictive role of TB in mRCC patients treated with targeted agents in prospective clinical trials. TB is able to predict prognosis independently to localization of metastases and prognostic class defined by MSKCC criteria, moreover it is strictly related to patient's performance status.
OBJECTIVE
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To investigate the possible prognostic role of baseline tumour burden (TB) in terms of progression‐free survival (PFS) and overall survival (OS), in patients with metastatic renal cell carcinoma (mRCC).
PATIENTS AND METHODS
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A homogenous group of patients with mRCC enrolled in second‐line trials post‐cytokine treatment were selected for the present analysis.
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The Response Evaluation Criteria in Solid Tumors (the sum of the longest unidimensional diameter of each target lesion) were used to assess TB.
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The PFS and OS rates were estimated using the Kaplan–Meier method and compared across the groups using the log‐rank test.
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The association between TB and PFS or OS was evaluated using a Cox proportional hazards model. Multivariable analyses were adjusted for other prognostic variables: the Memorial Sloan Kettering Cancer Centre (MSKCC) risk class and treatment.
RESULTS
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A total of 124 patients were included in the final analysis. Of these, 66% received sorafenib or sunitinib and 34% received placebo. The median follow‐up was 80.1 month.
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TB was directly related to PFS and OS and these associations remained significant after adjusting for modified MSKCC risk class and treatment,.
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Each 1‐cm increase in TB increased the risk of progression by 4.5% (hazard ratio HR: 1.05; 95% confidence interval CI 1.02–1.07; P < 0.001) and the risk of death by 5% (HR: 1.05; 95% CI 1.03–1.08; P < 0.001).
CONCLUSIONS
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TB is easy to calculate from standard computed tomography and significantly relates to OS in patients with mRCC.
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We report for the first time the independent prognostic role of baseline TB in multivariate analysis.
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We believe that this information could be translated into clinical practice.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background: The incidence of cervical cancer in pregnancy is estimated to be 1-10/10000 pregnancies. Approximately 3% of cervical
cancers are diagnosed during pregnancy. The incidence of abnormal Pap ...smears has been reported to be 5%-8%. Data on the spontaneous
evolution of an intraepithelial neoplasia during pregnancy are quite diverse. Of dysplasia cases diagnosed during pregnancy,
10%-70% regress and sometimes even disappear postpartum, while persistence in the severity of cervical neoplasia is reported
in 25%-47% and progression occurs in 3%-30%. However, adequate follow-up and definitive management in the postpartum period
is important. The objective of the study was to assess proper management of squamous intraepithelial lesion (SIL) during and
after pregnancy, to assess regression, persistence and risk of progression and the predictive role of HPV tests. Materials
and Methods: Thirty-one out of 721 pregnant women with a diagnosis of low- and high-grade SIL were observed. All patients
were triaged using standard colposcopy. The histological diagnosis was assessed by colposcopic direct biopsies. In patients
affected by high-SIL with colposcopic findings of suspected micro-invasive lesions, a loop electrosurgical excisional procedure
(LEEP) was carried out in pregnancy. High risk HPV tests were performed using PCR. The patients were followed up with cytology
and colposcopy every 6-8 weeks during gestation and nine weeks postpartum. They were re-evaluated using cytology, colposcopy
and histology for a final diagnosis and, when necessary, submitted to treatment. The patients were followed up for a minimum
of 5 years. The HPV test was performed once at 6-8 weeks during gestation and annually during the follow-up. Results: Of the
31 patients with abnormal cytology, histological analysis revealed 10 cervical intraepithelial neoplasia (CIN) 1, 5 CIN 2
and 16 CIN 3. The HPV test at diagnosis was positive for HPV 16 type in 22 cases and negative in 9. Five patients with CIN
2 and 11 with CIN 3 were followed up; 5 patients with CIN 3 with colposcopic findings of suspected microinvasive lesions were
submitted to an excisional procedure with LEEP before the 16th week of pregnancy. Conclusion: Performing high-risk HPV tests
may improve the follow-up of patients with SIL in pregnancy and postpartum in addition to cytology and colposcopy to indicate
persistence/progression of the lesions. Proper management and adequate follow-up could be proposed in pregnancy and postpartum.
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