Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed ...at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status.
We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series.
Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. 9% vs 18%, p = 0.019 and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant.
In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
•Hypersensitivity reactions (HSRs) to carboplatin are frequent in pretreated ovarian cancer (OC) patients (pts).•The role of BRCA mutations (mut) as a risk factor has been suggested.•We demonstrate that BRCAmut pts. have an increased risk of HSRs which is not justified by longer drug exposure only.•Receiving pegylated liposomal doxorubicin was a protective factor in our series.•The meta-analysis of literature, though results are heterogeneous, confirms the role of BRCAmut in increasing HSRs risk.
Abstract
Background
The prognostic value of the inflammatory indexes (eg. neutrophil-to-lymphocyte ratio, NLR; and systemic immune-inflammation index, SII) was demonstrated among patients with ...epithelial ovarian cancer (EOC). This study aimed to evaluate their predictive value in terms of platinum-free interval (PFI) as regard to bevacizumab treatment received.
Methods
A total of 375 EOC patients were retrospectively analyzed, 301 treated with chemotherapy alone and 74 with bevacizumab, with the decision to include this drug in the chemotherapy regimen left to the discretion of the treating physician. The correlation between NLR (defined as the ratio of neutrophil to lymphocyte count) and SII, calculated as (platelet count × neutrophil count)/lymphocyte count, and PFI were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Cutoff values were determined using Receiver Operating Characteristic (ROC) analysis.
Results
In univariate analysis, patients with high NLR (≥3) and SII (≥730) had a significantly shorter PFI at 6 and 12 months in overall cohort. In multivariate analysis, only NLR was an independent predictive factor for PFI at 6 months (OR = 2.52, 95% CI 1.30–4.87, p = 0.006) and at 12 months (OR = 2.05, 95% CI 1.05–4.01, p = 0.036) in the overall population and in the chemotherapy group (OR = 2.77, 95% CI 1.38–5.56, p = 0.004; HR = 2.27, 95% CI 1.10–4.70, p = 0.027, respectively). Inflammatory indexes were not predictive for PFI in the bevacizumab group (Table).
Table: 1020PPFI at 6 monthsPFI at 12 monthsN. ptsN. ptsOR (95% CI)pN. ptsN. ptsOR (95% CI)pNLR<3741391.00113981.00≥380682.52 (1.30-4.87)0.006106372.05 (1.05-4.01)0.036SII<73052991.0076731.00≥7301021080.74 (0.36-1.53)0.413143620.91 (0.45-1.84)0.786CTNLR<3621151.0098781.00≥369482.77 (1.38-5.56)0.00489242.27 (1.10-4.70)0.027SII<73041801.0063561.00≥73090830.76 (0.35-1.67)0.498124460.84 (0.39-1.82)0.663CT+BNLR<312241.0015201.00≥311200.47 (0.04-5.15)0.53817130.75 (0.11-5.25)0.774SII<73011191.0013171.00≥73012251.65 (0.13-20.56)0.69619161.78 (0.21-15.14)0.599
Conclusions
The NLR was an independent predictive factor for platinum-sensitivity in patients with EOC treated with chemotherapy. Its predictive role seems to be lost in patients treated with bevacizumab.
Legal entity responsible for the study
MITO group.
Funding
MITO group.
Disclosure
All authors have declared no conflicts of interest.
The prognostic value of the inflammatory indexes (eg. neutrophil-to-lymphocyte ratio, NLR; and systemic immune-inflammation index, SII) was demonstrated among patients with epithelial ovarian cancer ...(EOC). This study aimed to evaluate their predictive value in terms of platinum-free interval (PFI) as regard to bevacizumab treatment received.
A total of 375 EOC patients were retrospectively analyzed, 301 treated with chemotherapy alone and 74 with bevacizumab, with the decision to include this drug in the chemotherapy regimen left to the discretion of the treating physician. The correlation between NLR (defined as the ratio of neutrophil to lymphocyte count) and SII, calculated as (platelet count × neutrophil count)/lymphocyte count, and PFI were analyzed using logistic regression analyses adjusted for baseline patient characteristics. Cutoff values were determined using Receiver Operating Characteristic (ROC) analysis.
In univariate analysis, patients with high NLR (≥3) and SII (≥730) had a significantly shorter PFI at 6 and 12 months in overall cohort. In multivariate analysis, only NLR was an independent predictive factor for PFI at 6 months (OR=2.52, 95% CI 1.30–4.87, p=0.006) and at 12 months (OR=2.05, 95% CI 1.05–4.01, p=0.036) in the overall population and in the chemotherapy group (OR=2.77, 95% CI 1.38–5.56, p=0.004; HR=2.27, 95% CI 1.10–4.70, p=0.027, respectively). Inflammatory indexes were not predictive for PFI in the bevacizumab group (Table).Table: 1020PTable: 1020PPFI at 6 monthsPFI at 12 monthsN. ptsN. ptsOR (95% CI)pN. ptsN. ptsOR (95% CI)pNLR<3741391.00113981.00≥380682.52 (1.30-4.87)0.006106372.05 (1.05-4.01)0.036SII<73052991.0076731.00≥7301021080.74 (0.36-1.53)0.413143620.91 (0.45-1.84)0.786CTNLR<3621151.0098781.00≥369482.77 (1.38-5.56)0.00489242.27 (1.10-4.70)0.027SII<73041801.0063561.00≥73090830.76 (0.35-1.67)0.498124460.84 (0.39-1.82)0.663CT+BNLR<312241.0015201.00≥311200.47 (0.04-5.15)0.53817130.75 (0.11-5.25)0.774SII<73011191.0013171.00≥73012251.65 (0.13-20.56)0.69619161.78 (0.21-15.14)0.599
The NLR was an independent predictive factor for platinum-sensitivity in patients with EOC treated with chemotherapy. Its predictive role seems to be lost in patients treated with bevacizumab.
MITO group.
MITO group.
All authors have declared no conflicts of interest.
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