A randomized trial involving patients with metastatic prostate cancer whose disease progressed after receipt of docetaxel and hormonal therapy showed that cabazitaxel was superior to an ...androgen-signaling–targeted agent in extending imaging-based progression-free survival, overall survival, and PSA response.
In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant ...prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study.
CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice–web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form BPI-SF) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy—Prostate (FACT-P) questionnaire and the EuroQoL—5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling.
Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6–13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE–NE) with cabazitaxel and 8·5 months (4·9–NE) with abiraterone or enzalutamide (hazard ratio HR 0·55, 95% CI 0·32–0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0–NE) with cabazitaxel and 16·7 months (10·8–NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35–1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3–NE) with cabazitaxel and 8·9 months (6·3–NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44–1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060).
Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor.
Sanofi.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the CARD study (NCT02485691), cabazitaxel significantly improved median radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone/enzalutamide in patients with ...metastatic castration-resistant prostate cancer (mCRPC) who had previously received docetaxel and progressed ≤12 mo on the alternative agent (abiraterone/enzalutamide).
To assess cabazitaxel versus abiraterone/enzalutamide in older (≥70 yr) and younger (<70 yr) patients in CARD.
Patients with mCRPC were randomized 1:1 to cabazitaxel (25 mg/m2 plus prednisone and granulocyte colony-stimulating factor) versus abiraterone (1000 mg plus prednisone) or enzalutamide (160 mg).
Analyses of rPFS (primary endpoint) and safety by age were prespecified; others were post hoc. Treatment groups were compared using stratified log-rank or Cochran–Mantel-Haenszel tests.
Of the 255 patients randomized, 135 were aged ≥70 yr (median 76 yr). Cabazitaxel, compared with abiraterone/enzalutamide, significantly improved median rPFS in older (8.2 vs 4.5 mo; hazard ratio HR = 0.58; 95% confidence interval CI = 0.38–0.89; p = 0.012) and younger (7.4 vs 3.2 mo; HR = 0.47; 95% CI = 0.30–0.74; p < 0.001) patients. The median OS of cabazitaxel versus abiraterone/enzalutamide was 13.9 versus 9.4 mo in older patients (HR = 0.66; 95% CI = 0.41–1.06; p = 0.084), and it was 13.6 versus 11.8 mo in younger patients (HR = 0.66; 95% CI = 0.41–1.08; p = 0.093). Progression-free survival, prostate-specific antigen, and tumor and pain responses favored cabazitaxel, regardless of age. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 58% versus 49% of older patients receiving cabazitaxel versus abiraterone/enzalutamide and 48% versus 42% of younger patients. In older patients, cardiac adverse events were more frequent with abiraterone/enzalutamide; asthenia and diarrhea were more frequent with cabazitaxel.
Cabazitaxel improved efficacy outcomes versus abiraterone/enzalutamide in patients with mCRPC after prior docetaxel and abiraterone/enzalutamide, regardless of age. TEAEs were more frequent among older patients. The cabazitaxel safety profile was manageable across age groups.
Clinical trial data showed that cabazitaxel improved survival versus abiraterone/enzalutamide with manageable side effects in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and the alternative agent (abiraterone/enzalutamide), irrespective of age.
From the CARD study, we demonstrate that cabazitaxel improves efficacy outcomes versus abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer who had previously received docetaxel and progressed ≤12 mo on the alternative androgen receptor-targeted agent (abiraterone/enzalutamide), irrespective of age.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary ...tumor and metastasis pairs: 252 targeted gene sequencing, 152 RNA sequencing, 67 single nucleotide polymorphism arrays), we found a driver role for
and
somatic mutations. Metastases were enriched in
, and
mutations;
and
amplifications; and
deletions. An increase in clonality was observed in driver genes such as
and
. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-enriched switching was associated with
and/or
mutations. Metastases had lower immune score and increased immune-permissive cells. High tumor mutational burden correlated to shorter time to relapse in HR
/HER2
cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could affect treatment strategies in MBC. SIGNIFICANCE: The AURORA program, through the genomic and transcriptomic analyses of matched primary and metastatic samples from 381 patients with breast cancer, coupled with prospectively collected clinical data, identified genomic alterations enriched in metastases and prognostic biomarkers. ESCAT tier I/II alterations were detected in more than half of the patients.
.
Adjuvant endocrine therapy improves breast cancer survival, unconditional of other treatment. In premenopausal breast cancer, tamoxifen for 5 years is the standard treatment, with or without the ...addition of ovarian ablative therapy. The optimal timing and duration of ovarian ablative treatment is not yet defined, and it is not clear if there is additional benefit from ovarian suppression in combination with cytotoxic chemotherapy. With improving survival and excellent prognosis, there is increasing need for prevention of long-term adverse effects, monitoring and treatment when appropriate. Premature ovarian failure is frequent from adjuvant treatment of young breast cancer patients with a following risk of accelerated bone loss and infertility. The possible ovarian protective effect of ovarian ablation from luteinizing hormone-releasing hormone (LHRH) agonists is debated.Aims: The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor (ER) content. We also examine long-term side effects in regard to ovarian function and bone health.Patients and methods: The study was designed to determine whether the addition of the LHRH agonist goserelin and/or tamoxifen to adjuvant therapy provided benefit for premenopausal women with breast cancer. Patients were entered into a 2 x 2 factorial randomisation to tamoxifen 40 mg daily with or without concomitant goserelin, 3.6 mg every 28 days or goserelin alone for 2 years. Efficacy was analysed as well as the effects on ovarian function, bone mineral density and bone markers.A total of 927 women were recruited to the Stockholm part of the ZIPP trial. At a median follow-up of 12.3 years, goserelin reduced the risk of first event by 32% (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27% (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (P = 0.021) compared with no endocrine treatment. In highly ER-positive tumours, there were 29% fewer events among goserelin-treated patients (P = 0.044) and a trend towards greater risk reduction, depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In the study of ovarian function, 36% of the women in the goserelin group reported menses one year after completed CMF- and endocrine therapy, compared to 7% in the goserelin plus tamoxifen group, 13% in the tamoxifen group and 10% of the controls. Among women treated with goserelin, there was a statistically significant increase in the proportion of menstruating women one year after completed treatment, compared to at 24 months of treatment (P = 0.006), in contrast to all other treatment groups, who were unchanged or more often amenorrheic. The bone mineral study showed that after 2 years of treatment, there was a significant decline in bone mineral density (mean change, -5%; P < 0.001) in the women receiving goserelin. The combined goserelin and tamoxifen treatment, as well as tamoxifenalone, resulted in a lesser, but statistically significant, decrease in bone mineral density(mean change, -1.4%; P = 0.02; and -1.5%; P < 0.001).
The survival of patients with clear cell metastatic renal cell carcinoma (cc-mRCC) has improved substantially since the introduction of tyrosine kinase inhibitors (TKI). With the fact that TKIs ...interact with immune responses, we investigated whether polymorphisms of genes involved in immune checkpoints are related to the clinical outcome of cc-mRCC patients treated with sunitinib as first TKI.
Twenty-seven single-nucleotide polymorphisms (SNP) in
(PD-L1),
(PD-1), and
were tested for a possible association with progression-free survival (PFS) and overall survival (OS) in a discovery cohort of 550 sunitinib-treated cc-mRCC patients. SNPs with a significant association (
< 0.05) were tested in an independent validation cohort of 138 sunitinib-treated cc-mRCC patients. Finally, data of the discovery and validation cohort were pooled for meta-analysis.
rs231775 and
rs7866740 showed significant associations with OS in the discovery cohort after correction for age, gender, and Heng prognostic risk group HR, 0.84; 95% confidence interval (CI), 0.72-0.98;
= 0.028, and HR, 0.73; 95% CI, 0.54-0.99;
= 0.047, respectively. In the validation cohort, the associations of both SNPs with OS did not meet the significance threshold of
< 0.05. After meta-analysis,
rs231775 showed a significant association with OS (HR, 0.83; 95% CI, 0.72-0.95;
= 0.008). Patients with the GG genotype had longer OS (35.1 months) compared with patients with an AG (30.3 months) or AA genotype (24.3 months). No significant associations with PFS were found.
The G-allele of rs231775 in the
gene is associated with an improved OS in sunitinib-treated cc-mRCC patients and could potentially be used as a prognostic biomarker.
.
:
The optimal treatment of non‐Hodgkin's lymphoma (NHL) during pregnancy is currently undefined. The potential teratogenic effects of conventional chemotherapy preclude its use during the first ...trimester of pregnancy. We report the case of a pregnant woman with relapsed indolent follicular NHL who was treated with rituximab (unintentionally) during the first trimester. The treatment stabilised the disease. Following an uncomplicated pregnancy, a healthy child was born at full term and careful haematological and immunological monitoring has revealed no adverse effects resulting from exposure to rituximab. Data of using rituximab during pregnancy are scarce, but the present case shows that rituximab may be one option for treatment of NHL in early pregnancy.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
