Niraparib is an oral poly(adenosine diphosphate ADP-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of ...niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.
Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval CI, 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.
Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
Objective. To present Danish national survival data on women with early stage endometrial cancer and use these data to discuss the relevance of postoperative follow‐up. Design. Prospective study. ...Setting. Danish Endometrial Cancer Study (DEMCA). Population. Five hundred and seventy‐one FIGO stage IA (1988 classification) endometrial cancer patients prospectively included between 1986 and 1999. All patients had total abdominal hysterectomy and bilateral salpingo‐oophorectomy without adjuvant therapy. Methods. The patient and the disease characteristics were drawn from the DEMCA database with cross‐references to the national death registry and the national pathology database. Statistical methods included Kaplan–Meier, log‐rank and Cox regression analysis. Main outcome measures. Survival rates in relation to histopathology. Results. The five year overall survival rate was 88.9% and five year disease‐specific survival was 97.3%. Patients with low‐ (91.8%) and high‐risk histopathology (8.2%) were compared. The age‐adjusted overall and disease‐specific survival differed significantly between women with low‐ and high‐risk histopathology (p = 0.039 and p = 0.004, respectively). The disease‐specific survival adjusted for age between patients with well‐differentiated endometrioid tumors differed from those with moderately differentiated tumors (p = 0.008, hazard ratio = 3.75, 95% confidence interval 1.41–10.00). Recurrence data were available on 464 patients. Twenty‐three (3.9%) experienced recurrence. Of these recurrences, 15 of 23 (65%) were vaginal. Death from recurrence was observed in nine of 23 (39%) patients, and five of these nine had vaginal recurrences. Conclusions. Women with FIGO stage IA endometrial cancer have a very high disease‐specific five year survival. Survival was related to histopathology. Follow‐up at a highly specialized tertiary care center for patients with an extremely good prognosis may be questioned.
This randomized controlled trial (RCT) investigates differences in shoulder-related morbidity after delayed breast reconstruction by either a latissimus dorsi (LD) flap or a thoracodorsal artery ...perforater (TAP) flap.
In accordance with the CONSORT guidelines, we included women for unilateral delayed breast reconstruction. Patients were randomized to reconstruction by either of the two flaps. Shoulder-function was assessed at baseline and at 3, 6 and 12 months after surgery. The primary endpoint was patient-reported shoulder-related pain. A further objective assessment by the Constant Shoulder Score (CSS) was included as secondary endpoints.
A total of 50 women were enrolled over a two-year period and allocated to reconstruction, with 25 patients in each group. Patient-reported shoulder-related pain was significantly lower in the TAP group at 12 months after surgery when adjusting for pain at baseline: OR = 0.05 95%CI(0.005–0.51), p-value = 0.011.
The estimated effect on the total CSS at 12 months, when applying the TAP flap instead of the LD flap and adjusting for the baseline score, was 6.2 points with 95%CI(0.5–12.0), p-value 0.033. The TAP flap seems to have a statistically significant positive effect on pain and activity in daily life (ADL), while there were no significant effect on range of motion and strength after one year.
Patient reconstructed by the TAP flap are less likely to experience shoulder-related pain and have a better shoulder-function one year after the reconstruction. Harvest of the LD flap carries a higher risk of shoulder-function impairment, chronic pain and reduced ADL.
We report a study evaluating and comparing shoulder-related morbidity associated with delayed breast reconstruction using either the conventional latissimus dorsi (LD) flap or the thoracodorsal ...artery perforator (TAP) flap.
We conducted a retrospective cohort study of women over 18 years of age who had a unilateral, delayed breast reconstruction by either an LD or TAP flap at one center over a 56-month period. Shoulder function was assessed using the Constant Shoulder Score (CSS), which evaluated pain, activity of daily life (ADL), range of motion (ROM), and strength. A number of secondary outcomes were also examined.
Forty-nine women were included. Demographic and breast treatment data were comparable between the groups. The mean total CSS score for the reconstructed side of the TAP flap was statistically significantly better than that of the LD flap, with a difference of 10.9 points (95% confidence interval CI = 2.6–19.2, p-value 0.01). The mean total CSS score for the nonreconstructed side was not statistically significant between groups, with a difference of 0.1 points (95% CI = -6.1-6.2, p-value 0.98). The subscore analysis revealed that women reconstructed using the TAP flap had a difference of 3.2 points for pain (p-value 0.003) and 5.5 points for ROM (p-value 0.011). The factors ADL and strength were of equal magnitude in both groups.
Patients who undergo delayed breast reconstruction by the TAP flap seem less prone to suffer from postoperative pain and restricted ROM, thereby suggesting that this flap should be considered an advantageous alternative to the conventional LD flap. A randomized clinical trial is warranted to provide sufficient evidence to this statement.
We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.
We performed an open-label one-arm, two-stage, ...phase II study of 25 mg of oral exemestane in 51 patients with advanced (FIGO stage III-IV) or relapsed endometrioid endometrial cancer. Patients were stratified into subsets of estrogen receptor (ER) positive and ER negative patients.
Recruitment to the ER negative group was stopped prematurely after 12 patients due to slow accrual. In the ER positive patients, we observed an overall response rate of 10%, and a lack of progression after 6 months in 35% of the patients. No responses were registered in the ER negative patients, and all had progressive disease within 6 months. For the total group of patients, the median progression free survival (PFS) was 3.1 months (95% CI: 2.0-4.1). In the ER positive patients the median PFS was 3.8 months (95% CI: 0.7-6.9) and in the ER negative patients it was 2.6 months (95% CI: 2.1-3-1). In the ER positive patients the median overall survival (OS) time was 13.3 months (95% CI: 7.7-18.9), in the ER negative patients the corresponding numbers were 6.1 months (95% CI: 4.1-8.2). Treatment with exemestane was well tolerated.
Treatment of estrogen positive advanced or recurrent endometrial cancer with exemestane, an aromatase inhibitor, resulted in a response rate of 10% and lack of progression after 6 months in 35% of the patients.
Trial identification number (Clinical Trials.gov): NCT01965080.Nordic Society of Gynecological Oncology: NSGO-EC-0302.EudraCT number: 2004-001103-35.
Introduction
The aim of this study was to determine the proportion of patients who were referred to specialist care after reporting gynecological cancer alarm symptoms to their general practitioner. ...We sought to investigate whether contact with specialist care was associated with lifestyle factors or socioeconomic status.
Material and methods
Nationwide population‐based prospective cohort study in Denmark, based on a random sample of 51 090 women aged 20 years or older from the general population. A web‐based questionnaire regarding gynecological alarm symptoms and lifestyle was distributed to the invited individuals. Data about contact with specialist care were obtained from the National Patient Register and the National Health Insurance Service Registry, whereas information about socioeconomic status was collected from Statistics Denmark. Main outcome measures were percentages of patients having contact with specialist care and odds ratios (ORs) for associations between specialist care contact, lifestyle factors and socioeconomic status.
Results
The study included 25 866 nonpregnant women; 2957 reported the onset of at least one gynecological cancer alarm symptom, and 683 of these (23.1%) reported symptoms to their general practitioner. The proportion of individuals having contact with specialist care ranged from 39.3% (pain during intercourse) to 47.8% (bleeding during intercourse). Individuals with higher educational level had significantly higher odds of contact with a specialist (OR 1.86, 95% CI 1.17–2.95).
Conclusions
Educational level influences contact with specialist care among patients with gynecological cancer alarm symptoms. Future studies should investigate inequalities in access to the secondary healthcare system.
BACKGROUND Niraparib is an oral poly(adenosine diphosphate ADP-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the ...efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval CI, 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P < 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)
Niraparib, an inhibitor of poly(adenosine diphosphate ADP-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian ...cancer after platinum-based chemotherapy, regardless of the presence or absence of
mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.
In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.
Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval CI, 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.
Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of ...endometrial cancer.
We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed.
Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval CI, 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group.
Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.).
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