Table 2. Characteristics of studies of lung cancer approvals by the FDA from 2006 to 2018.
| Drug name (generic) | Approval date | N.st | Study design | Intervention arm | Control arm | Sample size | OS reported? | Primary endpoint | Effect size calculated (95%CI) | Magnitude of effect |
|---|---|---|---|---|---|---|---|---|---|---|
| Bevacizumab | Oct-06 | 1 | RCT open-label | bevacizumab+ carboplatin and paclitaxel | carboplatin and paclitaxel | 878 | Yes | OS | HR: 0.80 (NM) | Not large |
| Pemetrexed | Sep-08 | 1 | RCT open-label | pemetrexed + cisplatin | gemcitabine + cisplatin | 1725 | Yes | OS | HRa: 0.94 (0.84–1.05) | Not large a |
| Erlotinib | Apr-10 | 1 | RCT double-blind | erlotinib | placebo orally | 889 | Yes | PFS | HR: 0.71 (0.62–0.82) | Not large |
| Crizotinib | Aug-11 | 2.1 | A) Single-arm | crizotinib | no control | 136 | NM | ORR | RRc: 2.64 (2.15–3.24) | Large |
| Crizotinib | Aug-11 | 2.2 | B) Single-arm | crizotinib | no control | 119 | NM | ORR | RRc: 3.22 (2.67–3.88) | Large |
| Erlotinib | May-13 | 1 | RCT open-label | erlotinib | platinum-based doublet chemotherapy | 174 | Yes | PFS | HR: 0.34 (0.23–0.49) | Large |
| Afatinib | Jul-13 | 1 | RCT open-label | afatinib | pemetrexed/cisplatin | 345 | NM | PFS | HR: 0.58 (0.43–0.78) | Not large |
| Ceritinib | Apr-14 | 1 | Single-arm | certinib | no control | 163 | NM | ORR | RRc: 0.68 (0.55–0.83) | Not large |
| Ramucirumab | Dec-14 | 1 | RCT double-blind | ramucirumab+docetaxel | placebo+docetaxel | 1253 | Yes | OS | HR: 0.86 (0.75–0.98) | Not large |
| Nivolumab | Mar-15 | 2.1 | A) RCT open-label | nivolumab | docetaxel | 272 | Yes | OS | HR: 0.59 (0.44–0.79) | Not large |
| Nivolumab | Mar-15 | 2.2 | B) Single-arm | nivolumab | NA | 117 | NM | ORR | RRc: 1.71 (0.86–3.42) | Not large a |
| Gefitinib | Jul-15 | 2.1 | A) Single-arm | gefitinib | no control | 106 | NM | ORR | RRc: 2.64 (2.11–3.30) | Large |
| Gefitinib | Jul-15 | 2.2 | B) RCT open-label | gefitinib | carboplatin/paclitaxel | 186 | NM | PFS exA | HR: 0.54 (0.38–0.79) | Not large |
| Pembrolizumab | Oct-15 | 1 | Single-arm | pembrolizumab | no control | 61 | NM | ORR | RRc: 7.04 (3.06–16.19) | Large |
| Nivolumab | Oct-15 | 1 | RCT open-label | nivolumab | docetaxel | 582 | Yes | OS | HR: 0.73 (0.60–0.89) | Not large |
| Osimertinib | Nov-15 | 2.1 | A) Single-arm | osimertinib | no control | 201 | NM | ORR | RRc: 6.47 (4.75–8.82) | Large |
| Osimertinib | Nov-15 | 2.2 | B) Single-arm | osimertinib | no control | 210 | NM | ORR | RRc: 6.92 (5.10–9.39) | Large |
| Necitumumab | Nov-15 | 1 | RCT open-label | necitumumab+gemcitabine and cisplatin | gemcitabine and cisplatin (alone) | 1093 | Yes | OS | HR 0.84 (0.74–0.96) | Not large |
| Alectinib | Dec-15 | 2.1 | A) Single-arm | alectinib | no control | 87 | NM | ORR | RRc: 0.86 (0.63–1.18) | Not large a |
| Alectinib | Dec-15 | 2.2 | B) Single-arm | alectinib | no control | 138 | NM | ORR | RRc: 1.00 (0.77–1.29) | Not large a |
| Crizotinib | Mar-16 | 1 | Single-arm | crizotinib | no control | 50 | NM | ORR | RRc: 3.48 (2.76–4.39) | Large |
| Afatinib | Apr-16 | 1 | RCT open-label | afatinib | Erlotinib | 795 | Yes | PFS | HR: 0.82 (0.68–0.99) | Not large |
| Atezolizumab | Oct-16 | 2.1 | A)RCT open-label | atezolizumab | docetaxel | 1137 (Both studies A+B) | Yes | OS | HR: 0.74 (0.63–0.87) | Not large |
| Atezolizumab | Oct-16 | 2.2 | B) RCT open-label | atezolizumab | docetaxel | 1137 (Both studies A+B) | Yes | OS | HR: 0.69 (0.52–0.92) | Not large |
| Pembrolizumab | Oct-16 | 1 | RCT open-label | pembrolizumab | platinum-based chemotherapy | 305 | Yes | PFS | HR: 0.50 (0.37–0.68) | Large |
| Brigatinib | Apr-17 | 1 | Single-arm | brigatinib | no control | 110 | NM | OvRR | RRc: 1.27 (0.94–1.17) | Not large a |
| Pembrolizumab | May-17 | 1 | RCT open-label | pembrolizumab+pemetrexed and carboplatin | pemetrexed and carboplatin | 123 | NM | PFS | HR: 0.53 (0.31–0.91) | Not large |
| Dabrafenib and trametinib | Jun-17 | 1 | Single-arm | dabrafenib and trametinib | no control | 36 | NM | OvRR | RRc: 3.22 (2.72–3.81) | Large |
| Afatinib | Jan-18 | 1 | Single-arm | afatinib | no control | 32 (total of 3 studies) | NM | OvRR | RRc: 1.32 (0.97–1.81) | Not large a |
| Durvalumab | Feb-18 | 1 | RCT double-blind | durvalumab | placebo | 713 | Yes | PFS exA | HR: 0.52 (0.42–0.65) | Not large |
| Osimertinib | Apr-18 | 1 | RCT double-blind | osimertinib | gefitinib or erlotinib | 556 | NM | PFS exA | HR: 0.46 (0.37–0.57) | Large |
| Nivolumab | Aug-18 | 1 | Single-arm | nivolumab | no control | 109 | NM | OvRR | RRc: 1.70 (0.64–4.57) | Not large a |
| Dacomitinib | Sep-18 | 1 | RCT open-label | dacomitinib | gefitinib | 452 | Yes | PFS | HR: 0.59 (0.47–0.74) | Not large |
| Pembrolizumab | Oct-18 | 1 | RCT double-blind | pembrolizumab+ carboplatin and paclitaxel or nab-paclitaxel | placebo+carboplatin and paclitaxel or nab-paclitaxel | 559 | Yes | OS | HR 0.64 (0.49–0.85) | Not large |
| Lorlatinib | Nov-18 | 1 | Single-arm | lorlatinib | no control | 215 | NM | OvRR | RRc: 0.90 (0.72–1.14) | Not large a |
| Atezolizumab | Dec-18 | 1 | RCT open-label | atezolizumab + bevacizumab, paclitaxel, and carboplatin OR atezolizumab + paclitaxel, and carboplatin | bevacizumab, paclitaxel, and carboplatin | 800 | Yes | OS | HR: 0.78 (0.64–0.96) | Not large |
| Atezolizumab | Dec-18 | 1 | RCT open-label | atezolizumab | docetaxel | 850 | Yes | OS | HR: 0.74 (0.63–0.87) | Not large |
HR: hazard ratio, NM: not mentioned, OS: overall survival, OvRR: overall response rate, ORR: objective response rate, PFS: progressive-free survival, PFS exA: progressive-free survival with explanatory analysis, RCT: randomized controlled trial, RRc: risk ratio calculated.
a Not large and crossed the null effect.