PARP inhibitors (PARPi) have modest antitumor activity in patients with advanced breast cancer and mutation in BRCA. It is unclear whether some subgroups derive greater benefit from treatment. MEDLINE and EMBASE were searched from inception to March 2021 to identify trials of PARPi in patients with metastatic breast cancer. Objective response rate (ORR) and clinical benefit rate (CBR) to PARPi were extracted and pooled in a meta-analysis using the Mantel Haenszel random effects model. Meta-regression explored the influence of patient and tumor characteristics on ORR and CBR. For randomized trials, hazard ratio comparing PARPi to control therapy were pooled using inverse variance and random effects. Analysis included 43 studies comprising 2409 patients. Among these, 1798 (75%) patients had BRCA mutations and 1146 (48%) were triple negative. In 10 studies (28%; n = 680 patients), the PARPi was given in combination with platinum-based chemotherapy. Weighted mean ORR was 45%; 64% when combined with platinum vs 37% with PARPi monotherapy (p < 0.001). Previous platinum-based chemotherapy was associated with lower ORR (p = 0.02). Compared to standard chemotherapy, progression-free survival was improved (HR 0.64, p < 0.001), but there was no difference in overall survival (HR 0.87, p = 0.06). There were no differences in ORR or CBR between BRCA1 and BRCA2 mutations. PARPi are more active in combination with platinum than as monotherapy, with lower response if given as monotherapy after platinum exposure. Significant improvements in ORR translated to modest improvement in progression-free, but not overall survival. There was no association between ORR and BRCA mutations.
1545 Background: Early recognition and management of symptoms can improve outcomes in cancer patients receiving treatment. A number of randomized trials have investigated the effects of adding proactive symptom monitoring to usual care (UC). These include web-based, application-based, or telephone-based assessments. Results have been variable, and the impact of proactive symptom monitoring on QoL, treatment toxicity and utilization of unscheduled acute care remains unclear. Methods: A systematic search of MEDLINE identified prospective, randomized trials that studied the effect of proactive monitoring and intervention versus UC in cancer patients receiving chemotherapy. The difference between proactive symptom monitoring and UC on the mean and SD for QoL using validated scales was collected for each study and pooled in a meta-analysis. Analysis was performed using the standardized mean difference (SMD) using random-effects modeling. The effect size was reported as the Hedges’ adjusted g. We also calculated the odds ratios (OR) for the occurrence of several common symptoms of any grade in the individual trials and pooled them in a meta-analysis. Statistical significance was defined as P < 0.05. Quantitative significance was defined as a difference in QoL score exceeding the minimal clinically important difference (MCID) based on previous studies for each QoL framework. Results: Of the 17 trials which met eligibility criteria, FACT-G and EORTC QLQ C30 were the most consistently utilized QoL tools. The mean difference in score between intervention and control at the last evaluation visits was 2.82 (95% CI -0.57 to 6.21; P = 0.10) in FACT-G and 2.33 (95% CI -0.29 to 4.96; P = 0.08) in EORTC QLQ C30, neither of which met quantitative or statistical significance. There was a statistically significant reduction in fatigue (OR 0.67, 95% CI 0.46 to 0.97; P = 0.04), but no difference in constipation (OR 0.63, 95% CI 0.34 to 1.17; P = 0.15), nausea (OR 1.03, 95% CI 0.72 to 1.47; P = 0.89), pain (OR 0.83, 95% CI 0.62 to 1.10; P = 0.19), or diarrhea (OR 1.41, 95% CI 0.40 to 5.01; P = 0.60). SMD for symptom severity was calculated for fatigue, diarrhea, and nausea. Severity of fatigue was statistically lower with proactive symptom monitoring (SMD -0.45, 95% CI -0.69 to -0.22; I² = 0%, P < 0.001), however, magnitude of effect was modest. Conclusions: Proactive symptom monitoring in cancer patients receiving treatment is not associated with significant or meaningful QoL improvement. Similarly, there is limited impact on individual toxicity.
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