Table 2. Summary of trials on EGFR-TKIs combined with SBRT.
| Therapy | Study design | Case | Conditions | Treatment | Efficacy | AEs | Reference |
|---|---|---|---|---|---|---|---|
| EGFR-TKIs combined with concurrent SBRT | Phase III | 133 | Synchronous oligometastatic EGFR-mutated NSCLC | Control group: EGFR-TKI (gefitinib, erlotinib, icotinib) alone. Experimental group: EGFR-TKI + RT (25–40 Gy in 5 fractions), upfront RT before first-line EGFR-TKI | mPFS 12.5 vs. 20.2 months (P<0.001); mOS 17.4 vs. 25.5 months (P<0.001) | Grade 3–4 pneumonitis 6% | (40) |
| Phase II | 10 | Stage IV NSCLC harboring EGFR activating mutations | EGFR-TKI (erlotinib 150 mg or gefitinib 250 mg per day), thoracic radiotherapy (54–60 Gy/27–30 fractions/5.5–6 weeks) | 1-year PFS rate 57.1%, mPFS 13 months, median time to progression of irradiated lesion 20.5 months, ORR 50%, DCR 100% | Radiation pneumonitis (20%), rash (10%) | (41) | |
| Systemic therapy combined with consolidative SBRT | Phase II | 62 | Stage IV NSCLC with no more than 5 metastatic foci | Control group: first-generation EGFR-TKIs alone. Study group: SBRT (30–50 Gy in 5 fractions) after EGFR-TKI administration in patients who had achieved SD or PR | mPFS 9.0 vs. 17.6 months (HR =0.52; 95% CI: 0.31–0.89; P=0.02); mOS 23.2 vs. 33.6 months (HR =0.53; 95% CI: 0.30–0.95; P=0.03) | Grade 2 AEs: control group 45.2%, study group 50%; no grade 3 AEs | (42) |
| Phase II | 49 | Oligometastatic NSCLC without progression after first-line systemic therapy with ≤3 metastatic lesions | MT/O: maintenance treatment alone. LCT: radiotherapy or resection; chemotherapy 84%, TKI 16% | mPFS 3.9 months (95% CI: 2.3–6.6) vs. 11.9 months (95% CI: 5.7–20.9) (HR =0.35; 95% CI: 0.18–0.66; P=0.0054) | Control group: fatigue (n=1), anemia (n=1); experimental group: esophagitis (n=2), anemia (n=1), pneumothorax (n=1), abdominal pain (n=1) | (19) | |
| Phase II | 49 | Oligometastatic NSCLC without progression after first-line systemic therapy with ≤3 metastatic lesions | MT/O: maintenance treatment alone. LCT: radiotherapy or resection; chemotherapy 84%, TKI 16% | mPFS 4.4 months (95% CI: 2.2–8.3) vs. 14.2 months (95% CI: 7.4–23.1), P=0.02. mOS 17.0 months (95% CI: 10.1–39.8) vs. 41.2 months (95% CI: 18.9–not reached), P=0.02 | No additional grade 3 or greater toxicities | ||
| Phase II | 47 | Oligometastatic NSCLC without progression after first-line systemic therapy with ≤5 metastatic lesions | Single-arm: SABR (45–60 Gy in 3–5 fractions). Consolidative therapy after front-line systemic therapy (chemotherapy 61.7%, TKI 38.3%) | mPFS 34.3 months (95% CI: 31.1–38.8) | Pneumonitis: grade 1, 79.5%; grade 2, 12.8%; grade 3, 7.7% | (43) | |
| Retrospective | 122 | Older adult patients with oligometastatic EGFR-mutated NSCLC | TKI alone group: TKI monotherapy. TKIs + LCRT group: TKI combined with local consolidative radiation therapy | mPFS 12 months (95% CI: 11.05–12.95) vs. 17 months (95% CI: 15.37–18.63), P<0.001. mOS 29 months (95% CI: 26.86–31.14) vs. 38 months (95% CI: 35.61–40.39), P<0.001 | TKI + LCRT group: grade 1–2 pneumonia, 26%; grade 3, pneumonia 6% | (44) | |
| Retrospective | 194 | Synchronous oligometastatic NSCLC with ≤3 metastatic lesions | LCT: radiotherapy, surgical therapy, or other local ablative therapy | Comprehensive LCT (MST 29.2 months, 95% CI: 25.2–42.3; 1-year OS: 85.0%; 3-year OS: 42.7%; 5-year OS: 32.0%). All other patients (MST 22.9 months: 95% CI: 16.2–35.1; 1-year OS: 72.2%; 3-year OS: 34.6%; 5-year OSL: 18.9%) | NA | (45) | |
| Retrospective | 145 | Synchronous oligometastatic EGFR-mutated NSCLC | Consolidative LAT: all-LAT, part-LAT, non-LAT (surgery, radiotherapy) | mPFS in the all-LAT, part-LAT, and non-LAT groups of 20.6, 15.6, and 13.9 months, respectively (P<0.001). mOS in the all-LAT, part-LAT, and non-LAT groups of 40.9, 34.1, and 30.8 months, respectively (P<0.001) | Grade ≥3 pneumonitis (7.7%), esophagitis (16.9%) | (46) | |
| Retrospective | 231 | Oligometastatic EGFR-mutated lung adenocarcinoma | Monotherapy group: EGFR-TKI alone. Combination group: EGFR-TKI + LCT (surgery, radiotherapy) | mPFS 10 months (95% CI: 8.936–11.064) vs. 15 months (95% CI: 13.611–16.389) (HR =0.610; 95% CI: 0.461–0.807; P<0.001); mOS 21 months (95% CI: 18.445–23.555) vs. 34 months (95% CI: 27.889–40.111) (HR =0.593; 95% CI: 0.430–0.817; P=0.001) | NA | (47) | |
| Retrospective | 40 | Oligometastatic EGFR-mutated NSCLC | SBRT with a median BED10 value of 102.7 Gy (94.5–113.5 Gy) | mOS 40 months (95% CI: 32.562–47.438); 1-, 2-, and 3-year OS rates of 100.0%, 72.5%, and 62.5%, respectively; 1-, 2-, and 3-year PFS rates of 65.0%, 10.0%, and 0%, respectively | Grade 1–2: 36 (90.0%), Grade 3: 2 (5.0%), CTCAE v. 5.0 | (48) |
SBRT, stereotactic radiation therapy; SABR, stereotactic ablative radiotherapy; NSCLC, non-small cell lung cancer; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; LCT, local consolidative therapy; LCRT, local consolidative radiation therapy; LAT, local ablative therapy; RT, radiation therapy; MT/O, maintenance therapy or observation; mPFS, median progression-free survival; mOS, median overall survival; ORR, objective response rate; CI, confidence interval; HR, hazard ratio; MST, median survival time; CTCAE, Common Terminology Criteria for Adverse Events; DCR, disease control rate; SD, stable disease; PR, partial response; AEs, adverse events.