Shanghai Pulmonary Hospital, Tongji University, Shanghai, China
Caicun Zhou , Fumio Imamura , Ying Cheng , Isamu Okamoto , Byoung Chul Cho , Meng Chih Lin , Margarita Majem , Oliver Gautschi , Jhanelle Elaine Gray , Michael J. Boyer , Juliann Chmielecki , Ryan Hartmaier , Krishna Bulusu , J Carl Barrett , Rachel Hodge , Matilde Saggese , Astrid McKeown , Suresh S. Ramalingam
Background: In the Phase III FLAURA trial (NCT02296125), osimertinib, a third generation EGFR-TKI, showed superior efficacy to comparator EGFR-TKIs as first line treatment for EGFR mutation-positive (EGFRm) advanced NSCLC. In an exploratory analysis, we investigated clinical outcomes associated with detection of plasma EGFRm at 3 or 6 weeks (wks) after start of treatment. Methods: Treatment-naïve patients (pts) with EGFRm (ex19del or L858R) locally advanced or metastatic NSCLC were randomized 1:1 to receive osimertinib 80 mg once daily (QD) or comparator EGFR-TKIs (gefitinib 250 mg QD or erlotinib 150 mg QD). Plasma EGFR mutation analysis was conducted at baseline (BL), wks 3 and 6 by droplet digital PCR. Clearance was defined as undetectable levels of EGFRm in ctDNA at wks 3/6, where they were detectable at BL. Progression-free survival (PFS) was investigated based on early clearance of EGFRm. Results: In total 489/556 (88%) pts (osimertinib: 244/279; comparator: 245/277) had evaluable ctDNA at BL and wks 3/6. Of these, 342/489 (70%; osimertinib: 168/244; comparator: 174/245) had detectable BL EGFRm and were included in this analysis. See table. Conclusions: Clearance of plasma EGFRm after 3/6 wks of EGFR-TKI therapy was associated with a numerical improvement in PFS. The efficacy of osimertinib was superior to comparator EGFR-TKIs regardless of clearance status. Clinical trial information: NCT02296125
Osimertinib + Comparator EGFR-TKIs | Wk 3 | Wk 6 | ||
---|---|---|---|---|
D EGFRm (n = 126) | ND EGFRm (n = 208) | D EGFRm (n = 69) | ND EGFRm (n = 258) | |
mPFS, mo (95% CI) | 9.5 (7.0, 10.9) | 13.5 (11.1, 15.2) | 8.3 (6.8, 10.9) | 13.5 (11.1, 15.2) |
D EGFRm | Osimertinib (n = 56) | Comparator (n = 70) | Osimertinib (n = 30) | Comparator (n = 39) |
mPFS, mo (95% CI) | 11.3 (9.5, 16.5) | 7.0 (5.6, 8.3) | 11.1 (6.8, 13.8) | 8.2 (5.5, 9.9) |
HR (95% CI); p value | 0.50 (0.3, 0.8); p = 0.001 | 0.70 (0.4, 1.2); p = 0.191 | ||
ND EGFRm | Osimertinib (n = 106) | Comparator (n = 102) | Osimertinib (n = 134) | Comparator (n = 124) |
mPFS, mo (95% CI) | 19.8 (15.1, NC) | 10.8 (9.7, 11.1) | 19.8 (15.1, NC) | 10.2 (9.5, 11.1) |
HR (95% CI); p value | 0.41 (0.3, 0.6); p < 0.0001 | 0.40 (0.3, 0.6); p < 0.0001 |
CI, confidence interval; D, detectable; HR, hazard ratio; mo, months; mPFS, median PFS; NC, non-calculable; ND, non-detectable
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