Table 2.
Dose reduction and discontinuation rates for selected anticancer drugs
| Drug classification, trial name (indication) | n | Starting dose | Grade 3-4 AEs | Dose reduction rate | Discontinuation rate (for toxicity) | ORR | Sex moderation | |
|---|---|---|---|---|---|---|---|---|
| Male | Female | |||||||
| ALK inhibitors | ||||||||
| ALEX, Phase III (ALK-positive NSCLC; First line treatment [1L]) (70) | 303 | |||||||
| Alectinib vs | 600 mg bid | 41% | 16% | 11% | 83% | 45% | 55% | |
| Crizotinib | 600 mg bid | 50% | 21% | 13% | 76% | 42% | 58% | |
| BRAF + MEK inhibitors | ||||||||
| COMBI-d, Phase III (BRAF V600- positive melanoma, 1L) (71) | 423 | |||||||
| Dabrafenib + placebo vs | 150 mg bid | 30% | NR | 7% | 53% | 54% | 46% | |
| Dabrafenib + trametinib | 150 mg bid + 2mg qd | 32% | 11% | 69% | 53% | 47% | ||
| COLUMBUS, Phase III (BRAF V600-positive melanoma, 1L) (72) | 577 | |||||||
| Encorafenib + binimetinib vs | 450 mg qd + 45 mg bid | 34% | 48% | 6% | 63% | 60% | 40% | |
| Encorafenib vs | 300 mg qd | 34% | 70% | 10% | 51% | 56% | 44% | |
| Vemurafenib | 960 bid | 37% | 61% | 14% | 40% | 58% | 42% | |
| EGFR inhibitors | ||||||||
| LUX-Lung 3, Phase III (EGFR mutant NSCLC; 1L) (73) | ||||||||
| Afatinib vs chemotherapy | 345 | 40 mg qd | 49% | NR | 8% | 56% | 36% | 63% |
| EURTAC, Phase III (EGFR mutant NSCLC; 1L) (74) | ||||||||
| Erlotinib vs chemotherapy | 174 | 150 mg qd | 45% | 21% | 13% | 58% | 33% | 67% |
| FLAURA, Phase III (EGFR mutant NSCLC; 1L) (75) | 556 | |||||||
| Osimertinib vs | 80 mg qd | 34% | 4% | 13% | 80% | 36% | 63% | |
| Erlotinib/Gefitinib | 140 mg qd/250 mg qd | 45% | 5% | 18% | 76% | 38% | 62% | |
| VEGFR inhibitors | ||||||||
| SELECT, Phase III (thyroid cancer; 1L) (76) | 261 | 24 mg qd | ||||||
| Lenvatinib vs placebo | 24 mg qd | 76% | 68% | 14% | 69% | 48% | 52% | |
| REFLECT, Phase III (HCC; 1L) | 954 | |||||||
| Lenvatinib vs | 12 mg qd for ≥60 kg or 8 mg qd for <60 kg | 57% | 37% | 9% | 24% | 85% | 15% | |
| Sorafenib | 400 mg bid | 49% | 38% | 7% | 9% | 84% | 16% | |
| COMPARZ, Phase III (RCC; 1L) (77) | 1110 | |||||||
| Pazopanib vs | 800 mg qd | 74% | 44% | 24% | 31% | 71% | 29% | |
| Sunitinib | 50 mg qd, 4 weeks on/2 weeks off | 74% | 51% | 20% | 25% | 75% | 25% | |
| METEOR, Phase III (RCC; Second or further line treatment [2L]) (78) | 658 | |||||||
| Cabozantinib vs | 60 mg qd | 68% | 60% | 9% | 21% | 77% | 23% | |
| Everolimus | 10 mg qd | 58% | 25% | 10% | 5% | 74% | 26% | |
| PARP inhibitors | ||||||||
| PROfound, Phase III (mCRPC with BRCA1, BRCA2, ATM mutation, ≥2L) (79) | 387 | |||||||
| Olaparib | 300 mg bid | 51% | 22% | 18% | 33% | 100% | 0% | |
| SOLO-3, Phase 3 (ovarian cancer with BRCA mutation, ≥Third or further line treatment [3L]) (80) | ||||||||
| Olaparib vs chemotherapy | 266 | 300 mg bid | 50% | 27% | 7% | 72% | 0% | 100% |
Abbreviations: AEs, adverse events; bid, twice a day; n, patient sample size; NSCLC, non–small cell lung cancer; HCC, hepatocellular carcinoma; RCC, renal cell carcinoma; mCRPC, metastatic castration resistant prostate cancer; NR, not reported; ORR, overall response rate; qd, every day.