carboplatin
Regulatory sources consulted
Approved indications
- Advanced epithelial ovarian carcinoma, as first- or second-line treatment.
- Small cell lung cancer in combination with other antineoplastic agents.
- Advanced squamous cell carcinoma of the head and neck in combination chemotherapy.
- Neoadjuvant treatment of invasive bladder carcinoma and treatment of advanced disease within combination chemotherapy regimens.
Contraindications
Absolute
- Hypersensitivity to carboplatin or other platinum compounds.
- Pre-existing severe renal impairment with CrCl <30 mL/min, except an exceptional benefit-risk decision under the CIMA label.
- Severe myelosuppression.
- Tumors with significant bleeding.
- Concomitant yellow fever vaccination.
Clinical warnings
- Boxed warning · Myelosuppression is dose-dependent and can cause infection or bleeding; anemia is cumulative and may require transfusion. Monitor blood counts frequently and do not repeat until recovery. — DailyMed, Carboplatin injection set_id 4c89cedc-e48b-445c-ad05-54dbe60e4fb0
- Boxed warning · It can cause anaphylactic reactions within minutes, especially after prior platinum exposure. Administer where epinephrine, corticosteroids, antihistamines, and immediate support are available. — DailyMed, Carboplatin injection set_id 4c89cedc-e48b-445c-ad05-54dbe60e4fb0
- Major warning · Hemolytic uremic syndrome can be fatal. Discontinue at the first sign of microangiopathic hemolytic anemia, thrombocytopenia, or kidney deterioration; dialysis may be required. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
- Major warning · It can cause neurotoxicity, ototoxicity, and visual loss, with greater risk in patients older than 65, after prior cisplatin, at high doses, or with other ototoxic drugs. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
- Major warning · Secondary leukemia, myelodysplastic syndrome, hemolytic anemia, and hepatic veno-occlusive disease have been reported. Investigate persistent cytopenias or liver abnormalities. — AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123
Drug interactions
- HighOther myelosuppressive treatments or radiotherapy
Mechanism: Myelosuppression can increase additively.
Recommendation: Coordinate dose and schedule and closely monitor blood counts.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- HighAminoglycosides and loop diuretics
Mechanism: They can increase nephrotoxicity and ototoxicity.
Recommendation: Avoid when possible; if combined, intensify renal and hearing monitoring.
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
- ModerateOral anticoagulants
Mechanism: Chemotherapy can variably alter anticoagulation.
Recommendation: Monitor INR more frequently.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- ModeratePhenytoin or fosphenytoin
Mechanism: It can reduce anticonvulsant absorption or concentration and compromise seizure control.
Recommendation: Monitor concentrations and clinical response; consider a non-inducing anticonvulsant.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- HighCyclosporine, tacrolimus, or sirolimus
Mechanism: It can cause excessive immunosuppression with a risk of lymphoproliferation.
Recommendation: Avoid or coordinate close specialist monitoring.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
- HighLive vaccines
Mechanism: Immunosuppression increases the risk of generalized vaccine infection; yellow fever vaccine is contraindicated.
Recommendation: Avoid live vaccines and do not administer yellow fever vaccine.
AEMPS CIMA, CARBOPLATINO PHARMACIA, registro 62123https://cima.aemps.es/cima/dochtml/ft/62123/FT_62123.html
Adverse events
Common (≥1%)
thrombocytopenia · neutropenia · leukopenia · anemia · nausea · vomiting · abdominal pain · electrolyte abnormalities
Rare but serious
fatal infection or bleeding · hemolytic uremic syndrome · hemolytic anemia · secondary leukemia or myelodysplastic syndrome · anaphylaxis · posterior reversible encephalopathy syndrome
Pregnancy and lactation
FDA category: D
FDA Pregnancy Category D: it can cause embryo-fetal harm; avoid pregnancy and explain the risk if exposure occurs. It may irreversibly impair fertility. The CIMA label advises male contraception during treatment and for 4 months afterward and consideration of sperm preservation. The local evidence does not preserve a usable breastfeeding recommendation.
Recent literature (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