carboplatin
Sources réglementaires consultées
Indications approuvées
- Carcinome épithélial avancé de l’ovaire, en première ou deuxième ligne.
- Cancer du poumon à petites cellules en association à d’autres antinéoplasiques.
- Carcinome épidermoïde avancé de la tête et du cou en polychimiothérapie.
- Traitement néoadjuvant du carcinome invasif de la vessie et traitement de la maladie avancée dans des protocoles de polychimiothérapie.
Contre-indications
Absolues
- Hypersensibilité au carboplatine ou à d’autres composés du platine.
- Insuffisance rénale sévère préexistante avec ClCr <30 ml/min, sauf décision exceptionnelle bénéfice-risque selon la fiche CIMA.
- Myélosuppression sévère.
- Tumeurs avec saignement important.
- Vaccination concomitante contre la fièvre jaune.
Mises en garde cliniques
- Mise en garde encadrée · La myélosuppression dépend de la dose et peut entraîner infection ou hémorragie ; l’anémie est cumulative et peut nécessiter une transfusion. Surveiller fréquemment l’hémogramme et ne pas répéter avant récupération. — DailyMed, Carboplatin injection set_id 4c89cedc-e48b-445c-ad05-54dbe60e4fb0
- Mise en garde encadrée · Il peut provoquer des réactions anaphylactiques en quelques minutes, surtout après une exposition antérieure aux sels de platine. Administrer là où adrénaline, corticoïdes, antihistaminiques et support immédiat sont disponibles. — DailyMed, Carboplatin injection set_id 4c89cedc-e48b-445c-ad05-54dbe60e4fb0
- Mise en garde majeure · Le syndrome hémolytique et urémique peut être fatal. Arrêter au premier signe d’anémie hémolytique microangiopathique, de thrombopénie ou d’altération rénale ; une dialyse peut être nécessaire. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
- Mise en garde majeure · Il peut provoquer neurotoxicité, ototoxicité et perte visuelle, avec un risque accru après 65 ans, après cisplatine, à fortes doses ou avec d’autres médicaments ototoxiques. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
- Mise en garde majeure · Des leucémies secondaires, syndromes myélodysplasiques, anémies hémolytiques et maladies veino-occlusives hépatiques ont été rapportés. Explorer les cytopénies ou anomalies hépatiques persistantes. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
Interactions médicamenteuses
- SévèreAutres traitements myélosuppresseurs ou radiothérapie
Mécanisme: La myélosuppression peut augmenter de façon additive.
Recommandation: Coordonner dose et calendrier et surveiller étroitement l’hémogramme.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- SévèreAminosides et diurétiques de l’anse
Mécanisme: Ils peuvent augmenter la néphrotoxicité et l’ototoxicité.
Recommandation: Éviter si possible ; en cas d’association, renforcer la surveillance rénale et auditive.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.htmlDailyMed, Carboplatin injection set_id 4c89cedc-e48b-445c-ad05-54dbe60e4fb0https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c89cedc-e48b-445c-ad05-54dbe60e4fb0
- ModéréeAnticoagulants oraux
Mécanisme: La chimiothérapie peut modifier l’anticoagulation de façon variable.
Recommandation: Surveiller l’INR plus fréquemment.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- ModéréePhénytoïne ou fosphénytoïne
Mécanisme: Il peut réduire l’absorption ou la concentration de l’anticonvulsivant et compromettre le contrôle des crises.
Recommandation: Surveiller concentrations et réponse clinique ; envisager un anticonvulsivant non inducteur.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- SévèreCiclosporine, tacrolimus ou sirolimus
Mécanisme: Peut provoquer une immunosuppression excessive avec risque de lymphoprolifération.
Recommandation: Éviter ou coordonner une surveillance spécialisée étroite.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- SévèreVaccins vivants
Mécanisme: L’immunosuppression augmente le risque d’infection vaccinale généralisée ; le vaccin contre la fièvre jaune est contre-indiqué.
Recommandation: Éviter les vaccins vivants et ne pas administrer le vaccin contre la fièvre jaune.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
Effets indésirables
Communs (≥1%)
thrombopénie · neutropénie · leucopénie · anémie · nausées · vomissements · douleur abdominale · troubles électrolytiques
Rares mais graves
infection ou hémorragie mortelle · syndrome hémolytique et urémique · anémie hémolytique · leucémie secondaire ou syndrome myélodysplasique · anaphylaxie · syndrome d’encéphalopathie postérieure réversible
Grossesse et allaitement
Catégorie FDA: D
Catégorie D de la FDA : il peut provoquer une toxicité embryofœtale ; éviter la grossesse et expliquer le risque en cas d’exposition. Il peut altérer la fertilité de façon irréversible. La fiche CIMA conseille une contraception masculine pendant le traitement et pendant 4 mois après, ainsi que d’envisager la conservation du sperme. Les données locales ne conservent pas de recommandation exploitable sur l’allaitement.
Bibliographie récente (PubMed)
Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profi
Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55
Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).
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% an
Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advan