What are doublets used for in medical treatment?

Doublets in Medical Treatment: Applications in Cancer Therapy

Doublets are combination chemotherapy regimens consisting of two drugs used primarily for treating various cancers, including non-small cell lung cancer (NSCLC) and BRAF-mutant colorectal cancer, with evidence showing improved survival outcomes compared to single-agent therapy in specific patient populations.

Doublets in Non-Small Cell Lung Cancer (NSCLC)

Elderly Patients with NSCLC

• Doublet chemotherapy regimens have shown significant benefits in elderly patients (70-79 years) with stage IV NSCLC who have good performance status and limited comorbidities 1
• The combination of monthly carboplatin and weekly paclitaxel is specifically recommended for this population, showing improved overall survival compared to single-agent therapy 1
• In the IFCT-0501 trial, carboplatin plus paclitaxel demonstrated significantly longer median overall survival (10.3 months vs. 6.2 months) compared to single-agent therapy with either vinorelbine or gemcitabine 1

Types of Doublets in NSCLC

• Platinum-based doublets:
  • Carboplatin-based combinations (e.g., carboplatin + paclitaxel) have shown survival benefits in elderly patients 1
  • Cisplatin-based combinations (e.g., cisplatin + docetaxel) have shown mixed results in clinical trials 1
• Non-platinum doublets:
  • Combinations such as gemcitabine + vinorelbine or gemcitabine + taxane have been evaluated with variable results 1
  • Meta-analysis showed improved overall response rates but inconsistent survival benefits 1, 2

Efficacy Considerations

• Platinum-based doublets generally show better efficacy than non-platinum doublets:
  • Cisplatin-based doublets demonstrated improved 1-year survival compared to non-platinum doublets (RR=1.16) 3
  • Carboplatin-based doublets did not show statistically significant survival improvement over non-platinum doublets 3
• Response rates are typically higher with doublet therapy compared to single agents 2

Doublets in Colorectal Cancer

BRAF-Mutant Metastatic Colorectal Cancer

• The doublet combination of encorafenib plus cetuximab is now considered the standard of care for second- and third-line treatment of BRAF V600E-mutated metastatic colorectal cancer 1
• This doublet regimen was approved by the FDA and European Commission in 2020 for BRAF V600E-mutated metastatic colorectal cancer after prior therapy 1
• The BEACON CRC study demonstrated that encorafenib plus cetuximab significantly improved overall survival compared to control regimens (median OS 9.3 months vs. 5.9 months) 1

Doublets vs. Triplets in Cancer Treatment

Comparison in Colorectal Cancer

• In BRAF-mutant colorectal cancer, the addition of binimetinib to the encorafenib/cetuximab doublet (creating a triplet) showed similar efficacy but added toxicity 1
• Both doublet and triplet regimens significantly improved survival compared to standard therapy, but the doublet is generally preferred due to similar efficacy with less toxicity 1

Comparison in Multiple Myeloma

• Meta-analysis of triplet vs. doublet regimens in relapsed/refractory multiple myeloma showed triplets improved overall survival (HR 0.83) and progression-free survival (HR 0.68) 4
• However, triplet regimens were associated with higher rates of grade 3-4 adverse events compared to doublets 4

Safety Considerations

• Toxicity profiles differ between platinum and non-platinum doublets:
  • Cisplatin-based doublets: Higher risk of anemia, neutropenia, neurotoxicity, and nausea 3
  • Carboplatin-based doublets: Higher risk of anemia and thrombocytopenia 3
  • Non-platinum doublets: Generally better tolerated but may be less effective 2
• In elderly patients, doublet therapy is associated with increased toxicity compared to single-agent therapy, requiring careful patient selection 1

Clinical Decision Making

• For elderly NSCLC patients (70-79 years):
  • Good performance status and limited comorbidities: Consider carboplatin/paclitaxel doublet 1
  • Age ≥80 years: Benefits of chemotherapy are unclear and should be individualized 1
  • Poor performance status: Single-agent therapy may be preferred 1
• For BRAF V600E-mutated colorectal cancer:
  • After prior therapy: Encorafenib plus cetuximab doublet is recommended 1
  • Some subgroups may benefit more from triplet therapy, but this requires further validation 1

Common Pitfalls and Caveats

• Not all doublets are equally effective - platinum-based doublets generally show better efficacy than non-platinum doublets in NSCLC 3
• Patient selection is crucial - age alone should not preclude doublet therapy, but comorbidities and performance status should be considered 1
• Increased toxicity with doublets must be balanced against potential survival benefits 1, 2
• In some cancers like cervical carcinoma, non-platinum doublets may be preferred for patients previously treated with platinum-based therapy due to potential resistance 5