Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?

Purpose We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Materials and Method Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1–2 with the suspect drug. Results In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1–2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR ( p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms ( p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test ( p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). Conclusions We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.

Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence

Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.

Value of Skin Tests for Managing Hypersensitivity Reactions to Platinum Salts

Background: Platinum-based therapy continues to be one of the pillars of the treatment of different types of cancer. However, many times the responsible clinician renounces its use after the appearance of a hypersensitivity reaction.Objective: To assess the value of skin tests (ST) in clinical practice to address the treatment of patients with suspicion of immediate hypersensitivity reactions (HSRs) to platinum salts.Methods: Single-center retrospective study performed for 3 years. Adult patients treated with any platinum salt who experienced HSR symptoms and for whom an oncologist requested ST, were included. ST with cisplatin, carboplatin and oxaliplatin were performed. Results: Twenty-two patients were included. ST were positive in 12 patients (54.5%), of which 4 (33%) presented cross-reactivity to another platinum salt. Fifteen patients continued platinum-based chemotherapy: 9 patients with positive ST (4 continued by desensitization and 5 with another platinum) and 6 patients with negative ST, of which 1 repeated an HSR. A NPV of 0.91 was calculated. Conclusion: ST allowed accurate identification of platinum allergy patients and the resumption of platinum-based therapy in many patients for whom no suitable therapeutic alternative was clinically acceptable.

Gastrointestinal Disorders and Toxicities Induced By Anticancer Drugs. Another Risk Factor of Bleeding in Cancer-Associated Thrombosis

Introduction Anticancer treatments has been changing since decades, evolving from chemotherapy (platinum salts) to recent check-point inhibitors. Nausea, vomiting and diarrhoea are common adverse events of anticancer drugs, despites the fact that some supportive care drugs can manage these adverse events. Gastro-intestinal (GI) disorders/toxicities are also important. Such as gastric/duodenal ulcer, gastritis, stomatitis, colitis, esophagitis... Cancer-associated-thrombosis (CAT) patients were also reported to be exposed to such GI disorders/toxicities and several publications recommended to consider these GI disorders/toxicities when choosing an anticoagulant in CAT (Carrier M. Curr Oncol 2018; Moik F. ESMO Open 2020). However, little is known about the nature of the anticancer drugs that CAT patients are receiving. The aim of this work was to check all the anticancer's SmPCs (Summary of Product Characteristics) on the EMA website for GI disorders. Methods All SmPCs of anticancer drugs indicated for lung cancer were checked on the EMA website. All adverse events regarding GI disorders/toxicities were collected. The frequency of adverse events used was the following: very common (≥ 1/10); common (≥ 1/100 to &lt; 1/10); uncommon (≥ 1/1,000 to &lt; 1/100); rare (≥ 1/10,000 to &lt; 1/1000); very rare (&lt; 1/10,000). However, it was decided to mainly focus on very common and common ones. Old anticancer drugs SmPCs (platinium salts...) were checked on electronic medicines compendium (medicines.org.uk), because these old SmPCs are not always available on the EMA website. Generics, biosimilars and drugs without a licence were excluded. Results Twenty-eight anticancer drugs were identified with a mix of traditional chemotherapies (platinum salts...), tyrosine kinase inhibitors (nib) and monoclonal antibodies (mab). Among these 28 anticancer drugs, 26 had at least one very common/common GI disorders/toxicities. Obviously, vomiting (82.1%) and diarrhoea (89.3%) are very well-known, but it was interesting to see that many anticancer drugs were associated with other very common/common GI toxicities such as stomatitis (71.4%) and colitis (10.7%). Additionally, several drugs (35.7%) were exposing to GI bleeding and/or GI perforation but these last adverse events were less common. Unfortunately, the SmPCs did not include data about the GI profile of the patients during the trials. Conclusion Monreal M et al reported in 1991 that acute gastroduodenal lesion was found in 21% of patients with venous thromboembolism, but there are no dedicated study about the incidence of GI disorders in CAT patients. This work reported that GI disorders/toxicities were common in anticancer drug's SmPCs. Consequently, it is important to be aware of this before initiating an anticoagulant treatment. However, this work had limitations. Indeed, these adverse events were reported in the SmPCs, based mainly on cancer trials and not on CAT trials. Furthermore, clinical trials and SmPCs may not always reflect the real clinical setting. Finally, lung cancer patients are usually receiving anticancer regimens that include several anticancer drugs, so the potential impact of GI disorders/toxicities from 2 or 3 anticancer drugs on a single patients could be greater. Nevertheless, it sounds reasonable to check for GI disorders/toxicities risks in order to initiate an adequate anticoagulant treatment in CAT patients and during follow-up. Disclosures Janus: Guerbet:Research Funding;B-Braun:Honoraria;LEO Pharma A/S:Current Employment, Honoraria;Fresenius Medical Care:Honoraria;Amgen:Honoraria, Research Funding;TEVA:Research Funding;Daichii-Sankyo:Honoraria, Research Funding;Roche:Honoraria, Research Funding;Vifor Pharma:Honoraria, Research Funding;Gilead:Honoraria, Research Funding;Novartis:Honoraria;Pierre Fabre Oncology:Research Funding;Bayer:Honoraria, Research Funding;Pfizer:Consultancy, Honoraria;IPSEN:Honoraria.

Hypersensitivity to platinum salts according to BRCA status in ovarian cancer: Retrospective analysis of clinical outcomes.

6053 Background: Hypersensitivity reactions (HSRs) to platinum salts are an important issue in the treatment of ovarian cancer (OC) patients (pts). Few data suggest that, along with number of previous cycles, germline BRCA mutations could be a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum salts in a large group of OC pts with known BRCA status and correlated them with drug exposure time. Methods: Between March 2003 and September 2019, 432 pts with a diagnosis of OC and a known BRCA status, were recorded in our 5 Institutions and retrospectively analyzed. The following data were collected: histology, BRCA status, type of surgery and first line therapy, number of total lines and cycles received, line and cycle of HSR onset, symptoms, history of other allergies and if desensitization was attempted. We graded the severity of HSRs according to CTCAE v5.0. We calculated the total duration of exposure to platinum salts, summing up the duration of all platinum lines received by the pts. Results: Four hundred nine of 432 (94.7%) pts were treated with at least one platinum-based line of therapy and were eligible for the analysis. Among them, 314 pts were BRCA wild type (BRCAwt) (76.8%) and 95 were BRCA mutated (BRCAmut) (23.2%). There was no statistical difference in number of prior lines of therapy [median 1 (2-6) for BRCA wt and 2 (1-6) for BRCAmut pts (p = 0.194)] and duration of exposure to platinum [median 126 (42 – 893) and 197 (42 – 896) days for BRCAwt and BRCAmut pts, respectively (p = 0.145)]. Incidence of any grade HSRs was 29 / 314 (9.2%) among BRCAwt pts vs. 17/ 95 (17.9%) among BRCAmut pts (Odds ratio [OR] 0.47, 95% CI 0.24 – 0.89, p= 0.019). All recorded HSRs to platinum salts were related to carboplatin. We observed a numerically higher incidence of Grade 3-4 HSRs in BRCAmut pts (5.1% in BRCAwt vs. 10.5% in BRCAmut cohort, OR 0.46, 95% CI 0.20 – 1.04, p = 0.057). The risk to develop HSRs increases with duration of exposure to platinum, particularly in BRCAmut pts. The cumulative incidence of any grade HSRs was 20.6% vs. 23.3% after 12 months and 38.4% vs. 59.7% after 18 months in BRCAwt and BRCAmut pts, respectively (Hazard Ratio [HR] 1.72, 95% CI 0.94 – 3.12, p = 0.073). The cumulative incidence of severe HSRs was 10.9% vs. 15.7% after 12 months and 26.5% vs. 41.0% after 18 months in BRCAwt and BRCAmut pts, respectively (HR 1.88, 95% CI 0.85 – 4.16, p = 0.11). Conclusions: In BRCAmut OC pts, there is a significantly higher incidence of HSRs to carboplatin, that seems not justified by longer drug exposure only.