Neoadjuvant Chemotherapy (NACT)
Adding NACT before CCRT
- Da Costa SCS et al., JCO, 2019 (phase II, Cisplatin & Gemcitabine) – failed
- NAC-CCRT interval 3-4 weeks, 3 weekly cycle x 3
OUTBACK trial
(To be updated)
INTERLACE trial
- 장점: 항암 용량, 끝나자마자 RT한 점
- Cohort
- MFU 64m
- FIGO (2018) IB3-IIB 51%, IIIC1 40%
- Randomization
- IC+CCRT (n=250)
- CCRT alone (n=250)
- Outcome
- 5y-PFS 72% vs 64% / HR 0.65 (p=0.013)
- 5y-OS 80% vs 72% / HR 0.60 (p=0.015)
- Subgroup analysis
- Pattern of relapse
- Adverse events
- G3AEs 59% vs 48% (hematologic 30% vs 13%)
- Critics
- 다기관에서 RT plan에 대한 QC가 제대로 되었는지…
- RT rate 92% in CCRT alone (low… compliance가 보통은 반대 아닌가?) vs 97% in NACT+CCRT
- OS이 좋아진걸 정말 믿을 수 있을까? LC 2% 나빠지고 DM 5% 개선되었으나 Cx 10% 증가.. 해석에 주의가 필요할 것 같다.
- 비슷한 design 중 positive result를 보인 유일한 연구. 심지어 CIRCE trial은 반대 결과를 보임. 후속 연구가 필요.
- The INTERLACE trial underscores the importance of tight scheduling between NACT and CCRT, with careful control of overall treatment time.
- Andrade MO et al., Cancer Treat Rev., 2025
- Survival benefit with <6 weeks NACT / Platinum + Paclitaxel
아직 국내 (HIRA) 승인 안됨.
NACT+OP vs CCRT
NCT00193739 (JCO 2018) – failed, NACT-OP interval 3-4 weeks
EORTC-55994 (JCO 2023) – failed, NACT-OP interval 6 weeks
Immunotherapy
CALLA trial: durvalumab & FAILED
- IB2-IIB, N+ or IIIA-IVA (n=1060)
- Randomization
- CCRT with platinum + Durvalumab
- CCRT with platinum + Placebo
- Less immunogenic pts
- Pts with better prognosis
- Include node >1cm (lower risk) than KEYNOTE A18 (included ≥1.5cm)
- Control arm prognosis: better than expected (2yr-PFS 62%)
- Drug: PD-L1 inhibitor
Keynote 158: 2nd line
Keynote 826: 1st line in metastatic
KEYNOTE-A18: pembrolizumab & SUCCEEDED
- ‘ENGOT-cx11/COG-3047/KEYNOTE-A18’
- Cohort
- n=1060, IB2-IIB, N+ or IIIA-IVA (56%)
- LN short axis ≥1.5cm, Pelvic node ≥2, or PAN ≥1.
- Randomization
- CCRT with platinum + Pembrolizumab
- CCRT with platinum + Placebo
- Outcome
- 24m PFS: 68% vs. 57% / HR 0.70 (95% CI 0.55-0.89, p=0.0020)
- 24m OS not reached / HR 0.73 (95% CI 0.491.07, p not reached)
- PFS2 (positive impact on efficacy of next-line therapies) HR 0.65
- Challenges: Pts progressing after A18 are no longer IO-naïve -> limits the use of the KEYNOTE-826 regimen
Validation
- KCOG 1401
CALLA:
- Why FAILED?
Ongoing studies
- GX-188E (DNA vaccine) + Pembro
- Phase II for recurrent/metastatic Ca.