Table 2 Representative molecular response studies.
From: Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors
Author | Pub year | Cancer type | Treatment | ctDNA method | On-treatment ctDNA Time Point | PFS | OS | |||
|---|---|---|---|---|---|---|---|---|---|---|
Targeted therapy | ||||||||||
Kwon [38] | 2022 | NSCLC | Targeted therapy | NGS | 2 months | Median PFS | - | Median OS | - | |
HR | 0.29 (0.13–0.66) | HR | 0.23 (0.06–0.8) | |||||||
P-value | p = 0.0012 | P-value | p = 0.0307 | |||||||
Besse [40] | 2018 | NSCLC | Targeted therapy | NGS | 2 weeks (C1D15) | - | - | |||
Mack [37] | 2022 | NSCLC | Targeted therapy | NGS | 8 weeks | Median PFS | 15.1 vs 2.8 mos | Median OS | 27.2 vs 15.0 mos | |
HR | 0.24 (0.13–0.44) | HR | 0.30 (0.14–0.66) | |||||||
P-value | p = 0.00001 | P-value | p = 0.003 | |||||||
Iwama [33] | 2017 | NSCLC | Targeted therapy | NGS | 4 weeks | Median PFS | 4 wks: 14.3 vs 10.0 mos | - | ||
HR | - | |||||||||
P-value | p = 0.52 | |||||||||
Marchetti [32] | 2015 | NSCLC | Targeted therapy | ddPCR | 2 weeks, 2 months | - | - | |||
Paik [15] | 2020 | NSCLC | Targeted therapy | NGS | 6 weeks, 12 weeks | - | - | |||
Phallen [26] | 2018 | NSCLC | Targeted therapy | NGS | Median 19 days | Median PFS | 1.6 vs 13.7 mos | - | ||
HR | 66.6 (13.0–341.7) | |||||||||
P-value | p < 0.0001 | |||||||||
Shaw [23] | 2019 | NSCLC | Targeted therapy | NGS | 6 weeks | Median PFS | 6.6 vs 2.6 mos | Median OS | 18.0 vs 8.6 mos | |
HR | 2.6, 95% Cl: 1.2, 5.8 | HR | 2.0, 95% Cl: 0.9–4.6 | |||||||
P-value | - | P-value | - | |||||||
Shepherd [34] | 2018 | NSCLC | Targeted therapy | ddPCR | 3 or 6 weeks | Median PFS | 10.9 vs 5.7 mos | - | ||
HR | - | |||||||||
P-value | - | |||||||||
Wang [35] | 2018 | NSCLC | Targeted therapy | ddPCR | 8 weeks | Median PFS | 11.0 vs 2.1 mos | - | ||
HR | - | |||||||||
P-value | - | |||||||||
Zhou [14] | 2019 | NSCLC | Targeted therapy | ddPCR | 3 or 6 weeks | Median PFS | 19.8 vs 11.3 mos (osi); 10.8 vs 7.0 mos (comp) | - | ||
HR | - | |||||||||
P-value | - | |||||||||
Bidard [13] | 2019 | CRC | Targeted therapy | ddPCR | 6 weeks | - | Median OS | 18 vs 42 mos (for ctDNA (+) vs (-) pre-liver met resection) | ||
HR | - | |||||||||
P-value | p < 0.001 | |||||||||
Hong [48] | 2016 | CRC | Targeted therapy | ddPCR or NGS | 2 weeks | - | - | |||
Kopetz [49] | 2020 | CRC | Targeted therapy | NGS | 1st assessment | - | - | |||
Nakamura [19] | 2021 | CRC | Targeted therapy | NGS | 3 weeks | Median PFS | 5.0 vs 2.2 mos | Median OS | 16.5 vs 7.3 mos | |
HR | 0.30; 95% Cl, 0.13–0.72 | HR | 0.31; 95% Cl, 0.12–0.82 | |||||||
P-value | - | P-value | - | |||||||
Hrebien [51] | 2019 | Breast | Targeted therapy | Sequencing & ddPCR | Day 28 | Median PFS | Suppressed CDR28 11.1 mos vs. high CDR28 6.4 mos | - | ||
HR | 0.20 (0.08–0.5) | |||||||||
P-value | p < 0.0001 | |||||||||
MartÃnez-Sáez [30] | 2021 | Breast | Targeted therapy | NGS | 4 weeks | Median PFS | - | - | ||
HR | 0.39 (responders, mVAFR <0.3); 0.27 (non-responders, mVAFR >1) | |||||||||
P-value | p = 0.025 (responders, mVAFR <0.3); p = 0.010 (non-responders, mVAFR >1) | |||||||||
Modi [22] | 2020 | Breast | Targeted therapy | NGS | 9 weeks (C4D1) | Median PFS | 18.1 vs 6.2 mos | - | ||
HR | 3.55 (1.53-8.24) | |||||||||
P-value | p = 0.00309 | |||||||||
O’Leary [12] | 2018 | Breast | Targeted therapy | ddPCR | 2 weeks (C1D15) | Median PFS | - | - | ||
HR | 3.94 (1.61–9.64) | |||||||||
P-value | p = 0.0013 | |||||||||
Ma [52] | 2017 | Breast | Targeted therapy | NGS | 4 weeks | - | - | |||
Gray [53] | 2015 | Melanoma | Targeted therapy | ddPCR | 4–8 weeks | - | - | |||
Goodall [55] | 2020 | mCRPC | Targeted therapy | NGS | 8 weeks (C3D1) | Median PFS | - | - | ||
HR | 2 (1.3–3.2) | |||||||||
P-value | - | |||||||||
Jayaram [56] | 2021 | mCRPC | Targeted therapy | NGS | 4 weeks (C2D1) | Varied by gene tested, improved for patients who cleared vs did not clear mutation on-Tx | Varied by gene tested, improved for patients who cleared vs did not clear mutation on-Tx | |||
Parikh [16] | 2020 | GI | Targeted therapy | ddPCR | 4 weeks | Median PFS | 175 vs 59.5 days | - | ||
HR | 3.29; 95% Cl, 1.55–7.00 | |||||||||
P-value | p < 0.0001 | |||||||||
Maron [46] | 2020 | GE | Targeted therapy | NGS | 9 weeks | Median PFS | 12.3 vs 3.9 mos (in those with clearance vs not) | - | ||
HR | - | |||||||||
P-value | p = 0.02 | |||||||||
Maron [47] | 2019 | GE | Targeted therapy | NGS | <150 days after metastatic Dx | - | Median OS | 13.7 vs 8.6 mos | ||
HR | 0.3; 95% CI, 0.1–0.8 | |||||||||
P-value | p = 0.02 | |||||||||
Immunotherapy | ||||||||||
Ricciuti [44] | 2021 | NSCLC | Immunotherapy | NGS | 1st follow up | Median PFS | 30.6 vs 3.7 mos | Median OS | NR vs 16.2 mos | |
HR | - | HR | - | |||||||
P-value | - | P-value | - | |||||||
Cabel [21] | 2017 | NSCLC, CRC, Uveal mel | Immunotherapy | Bi-PAP, ddPCR or NGS | 8 weeks | Median PFS | 11 vs 2 mos for ctDNA undetectable vs detectable | Median OS | - | |
HR | - | HR | 15 for ctDNA undetectable vs detectable | |||||||
P-value | p = 0.001 | P-value | p = 0.004 | |||||||
Zhang [17] | 2020 | NSCLC, Solid tumors | Immunotherapy | NGS | 6–8 weeks | Median PFS | - | Median OS | - | |
HR | 0.28 (0.14–0.57) 0.22 (0.04–0.30) 0.3 (0.15–0.60) | HR | 0.29 (0.16–0.53) 0.12 (0.04–0.37) 0.29 (0.10, 0.84) | |||||||
P-value | - | P-value | - | |||||||
Assaf [20] | 2023 | NSCLC | Immunotherapy | NGS | 6 weeks | - | Median OS | 7.3 mos vs 25.2 mos | ||
HR | 3.28 (2.2–4.9) | |||||||||
P-value | p < 0.001 | |||||||||
Anagnostou [41] | 2019 | NSCLC | Immunotherapy | NGS | 4-8 weeks | Median PFS | - | Median OS | - | |
HR | - | HR | - | |||||||
P-value | p = 0.001 | P-value | p = 0.008 | |||||||
Goldberg [29] | 2018 | NSCLC | Immunotherapy | NGS | q2 or more weeks | NS due to small sample | Median OS | - | ||
HR | 0.11 (0.02–0.88) for those who cleared; 0.13 (0.03–0.51) for ctDNA responders | |||||||||
P-value | p = 0.037 (for those who cleared); p = 0.0034 (for ctDNA responders) | |||||||||
Leprieur [43] | 2018 | NSCLC | Immunotherapy | NGS | 2 months | Median PFS | 12 mos for pts with ctDNA decrease vs 0.7 mos with ctDNA increase >9% | Median OS | 2.2 mos for ctDNA conc >0.006 ng/ul vs NR for conc <0.006 ng/ul | |
HR | - | HR | - | |||||||
P-value | p < 0.001 | P-value | - | |||||||
Nabet [42] | 2020 | NSCLC | Immunotherapy | NGS | Various (median 2.4 weeks) | Median PFS | 22.4 vs 2.3 mos | - | ||
HR | 2.28 | |||||||||
P-value | p = 0.013 | |||||||||
Thompson [18] | 2021 | NSCLC | Immunotherapy | NGS | 9 weeks | Median PFS | 14.1 vs 4.4 mos | Median OS | NR [95% CI lower bound 22.1 mos] v 12.0 mos | |
HR | 0.25; 95% Cl, 0.13–0.50 | HR | 0.27; 95% Cl, 0.12–0.64 | |||||||
P-value | - | P-value | - | |||||||
Lee [11] | 2018 | Melanoma | Immunotherapy | ddPCR | Before week 12 | - | Median OS | - | ||
HR | wk 6 (n = 27) HR for favorable vs unfavorable ctDNA profile: 3.9 (2.1–14.0); wk 12 (n = 29) HR: 3.3 (1.0–10.5) | |||||||||
P-value | p = 0.02 (wk 6); p = 0.03 (wk 12) | |||||||||
Lee [54] | 2017 | Melanoma | Immunotherapy | Not described | Before week 12 | Grps A&B sig longer than grp C, but NR; Grp C 2.7 m | Grps A&B sig longer than grp C but NR, grp C 9.8 m | |||
Dawson [50] | 2013 | Breast | Immunotherapy | digital PCR or NGS | q3 or more weeks | - | - | |||
Kim [45] | 2018 | Gastric | Immunotherapy | NGS | 6 weeks | Median PFS | 123 vs 66 days | - | ||
HR | - | |||||||||
P-value | p = 0.029 | |||||||||
Bratman [58] | 2020 | Solid tumors | Immunotherapy | NGS | 6–7 weeks | Median PFS | - | Median OS | - | |
HR | 0.33 (0.19–0.58) | HR | 0.36 (0.18–0.71) | |||||||
P-value | - | P-value | - | |||||||
