Definition of Carboplatin Resistance in Non-Squamous NSCLC
The provided evidence does not contain a formal definition of "carboplatin-resistant" non-squamous NSCLC. The guidelines focus on treatment recommendations for various clinical scenarios but do not establish specific criteria (such as time to progression or treatment-free interval) that would classify a patient as carboplatin-resistant.
What the Evidence Actually Addresses
The ESMO guidelines and related evidence discuss:
- First-line treatment: Platinum-based doublet chemotherapy (including carboplatin) is standard for metastatic NSCLC with PS 0-2 1
- Second-line treatment after progression: Patients who progress after first-line platinum-based chemotherapy should receive second-line therapy, with options including pemetrexed (non-squamous only), docetaxel, or immune checkpoint inhibitors 1, 2
- Maintenance therapy: Continuation of pemetrexed after initial carboplatin-pemetrexed induction improves outcomes 2
Clinical Context from Related Disease States
While not directly addressing NSCLC, one study examined paclitaxel/carboplatin in small-cell lung cancer patients "resistant" to prior chemotherapy, defining resistance as relapse within 3 months after first-line treatment 3. However, this definition cannot be extrapolated to non-squamous NSCLC without supporting evidence.
Practical Approach When Carboplatin-Based Therapy Fails
When a patient with non-squamous NSCLC progresses on or after carboplatin-based chemotherapy:
- Perform comprehensive molecular testing for EGFR, ALK, ROS1, BRAF V600E, MET exon 14, RET, NTRK, and PD-L1 expression before initiating second-line therapy 2
- Preferred second-line options for PS 0-2 patients include immune checkpoint inhibitors (nivolumab, atezolizumab regardless of PD-L1; pembrolizumab if PD-L1 ≥1%) 1, 2
- Alternative second-line chemotherapy includes pemetrexed monotherapy (non-squamous only) or docetaxel 1, 2
Important Caveat
The term "platinum-resistant" or "carboplatin-resistant" is not formally defined in the major NSCLC guidelines reviewed 1. Treatment decisions are based on progression status, performance status, histology, and molecular markers rather than a specific resistance classification.