Table 2.
Second-line or later ICI Clinical Trials in EGFRm NSCLC.
| Trial | Phase | Intervention | Outcome | Safety | Reference | |
|---|---|---|---|---|---|---|
| ICI Monotherapy | ||||||
| KEYNOTE-010 | 3 | Pembrolizumab (P) vs docetaxel (D) | HR for PFS$ with P vs D: 1.79 in EGFRm vs 0.83 in EGFRwt HR for OS with P vs D: 0.88 vs 0.66 |
P: G3-5#: 13-16% D: G3-5: 35% |
(44) | |
| CheckMate 057 | 3 | Nivolumab (N) vs docetaxel (D) | HR for OS$ with N vs D: 1.18 for EGFRm vs 0.66 in EGFRwt | N: G3-5#: 10% D: G3-5: 54% |
(45) | |
| POPLAR | 2 | Atezolizumab (A) vs docetaxel (D) | HR for OS$ with A vs D: 0.99 for EGFRm vs 0.70 in EGFRwt | A: G3-4#: 40%, G5: 4% D: G3-4: 53%, G5: 4% |
(46, 47) | |
| KEYNOTE-001 | 1b | Pembrolizumab | PFS$: 6.0 mo in EGFRm vs 12.1 mo in EGFRwt | N.R.** | (48) | |
| PACIFIC | 3 | Durvalumab | HR for PD$ or death: 0.76 in EGFRm vs 0.47 in EGFRwt | TRAE: 96.8%, G3-4: 29.9% | (49) | |
| ATLANTIC | 2 | Durvalumab | ORR for EGFRm/ALKm: 3.6% PD-L1 TPS <25%, 12.2% for PD-L1 ≥25% OS for EGFRm/ALKm: 9.9 mo PD-L1 TPS <25%, 13.3 mo for PD-L1 ≥25% |
G3-4: 5% | (50) | |
| ICI + Chemotherapy | ||||||
| NCT03513666 | 2 | Toripalimab + PT-DC | ORR: 50% PFS: 7.0 mo |
G3-5: 55%, including neutropenia (48%), leukopenia (20%), and anemia (13%) | (51) | |
| ICI + EGFR TKI Therapy | ||||||
| CheckMate 012 | 3 | Nivolumab + erlotinib | ORR: 15%&
PFS: 5.1 mo OS: 18.7 mo |
G3: 24%, no G4-G5 | (52) | |
| TATTON | 1b | Durvalumab + osimertinib | ORR: 43% | TRAE: 100%, G3-5: 48%. ILD occurred in 22% with G≥3 ILD in 8.7% | (53) | |
| CAURAL | 3 | Durvalumab + osimertinib | ORR: 64% | TRAE: 100%, G3-5: 8%. One G2 ILD reported | (54) | |
| Dual ICI Therapy | ||||||
| KEYNOTE-021 | 1/2 | Pembrolizumab + ipilimumab | ORR: 10% for EGFRm vs 30% for EGFRwt | TRAE#: 98%, G3-G5: 49%, one G5 pancreatitis | (55) | |
| ICI + VEGF Inhibitor + Chemotherapy | ||||||
| IMpower150 | 3 | Atezolizumab (A) + bevacizumab (B) + carboplatin-paclitaxel (CP) | ORR##: 70.6% for ABCP, 35.6% for ACP, 41.9% for BCP OS: NR for ABCP##, 17.5 mo for BCP |
G3-4: 64% of ABCP, 68% of ACP, and 64% of BCP | (56) | |
| NCT03647956 | 2 | Atezolizumab + bevacizumab + pemetrexed-carboplatin | ORR: 62.5% PFS: 9.43 mo |
G3-5: 37.5%, One G5 myocardial infarction, 7.5% blood clot | (57) | |
Indicated categories of trials with respective trial parameters are given. ORR, overall response rate; TRAE, Treatment related adverse event; G, grade of toxicity. #TRAEs for entire study population and not selected for EGFRm patients. $ORR data not given for EGFRm subgroup. **Safety data were not reported in this long-term survival update report. PD, progressive disease; PT-DC, platinum-doublet chemotherapy. &Authors note that these patients were all TKI treated for first-line. NR, not reached. ##These numbers refer to the subgroup of patients with sensitizing EGFR mutations.