Abstract 388P
Background
The PARADIGM primary analysis demonstrated that PAN significantly improved OS vs BEV combined with mFOLFOX6 in RAS WT and left-sided mCRC. ETS and DpR are on-treatment prognostic factors related to favorable OS and PFS in mCRC chemotherapy. We report ETS and DpR and the correlation with OS and PFS in patients (pts) with RAS WT mCRC from PARADIGM.
Methods
Relative change in maximum tumor diameter was analyzed between baseline and 8 wks of treatment. ETS was defined as a ≥30% decrease in tumor size by investigator assessment. OS and PFS were compared in pts with/without ETS stratified by treatment arm and primary tumor location (left-sided, overall, right-sided). DpR was the maximum post-baseline percent decrease in the sum diameter of target lesions. No hypothesis was formally tested; P-values were based on a 2-sided stratified log-rank test and were descriptive. Cutoff date: Jan 14, 2022.
Results
A greater proportion of pts had ETS with PAN (left: 64.4%; overall: 58.5%) vs BEV (left: 38.0%; overall: 38.8%). Left-sided PAN pts with ETS showed longer OS (median: 42.6 vs 27.1 mo; HR: 0.56 [95% CI: 0.42–0.75]; P<0.001) and PFS (15.7 vs 9.6 mo; 0.62 [0.48–0.81]; P<0.001) than pts without ETS. Similarly, left-sided BEV pts with ETS had longer OS (median: 41.3 vs 32.4 mo; HR: 0.69 [95% CI: 0.52–0.91]; P=0.01) and PFS (14.5 vs 11.5 mo; 0.81 [0.62–1.06]; P=0.094). Right-sided PAN pts with ETS had longer OS, but not BEV (Table). Left-sided and overall PAN groups had greater median DpR than BEV (left, -59.4 vs -43.6; overall, -57.3 vs -43.6), with no difference between right-sided arms.
Conclusions
Although ETS was associated with favorable survival outcomes in both arms, PAN achieved more ETS and greater DpR than BEV in left-sided pts. In right-sided pts, ETS was only predictive with PAN, warranting further biomarker analysis to predict PAN benefit. Table: 388P
| OS | PAN + mFOLFOX6 | BEV + mFOLFOX6 | ||
| ETS ≥30% | ETS <30% | ETS ≥30% | ETS <30% | |
| Left | n=201 | n=111 | n=111 | n=181 |
| Median (95% CI), mo | 42.6 (37.5–49.7) | 27.1 (21.8–36.3) | 41.3 (31.6–46.5) | 32.4 (27.9–36.8) |
| HR 95% CI P value | 0.56 0.42–0.75 <0.001 | 0.69 0.52–0.91 0.010 | ||
| Overall | n=234 | n=166 | n=156 | n=246 |
| Median (95% CI), mo | 42.1 (37.5–48.4) | 23.1 (17.7–31.0) | 33.8 (29.3–41.3) | 30.5 (26.9–34.0) |
| HR 95% CI P value | 0.50 0.39–0.64 <0.001 | 0.78 0.62–0.99 0.036 | ||
| Right | n=30 | n=54 | n=42 | n=61 |
| Median (95% CI), mo | 34.1 (21.0–42.2) | 15.2 (11.3–20.2) | 22.3 (17.4–30.9) | 25.5 (16.9–31.6) |
| HR 95% CI P value | 0.47 0.28–0.79 0.005 | 0.94 0.60–1.45 0.746 |
Clinical trial identification
NCT02394795.
Editorial acknowledgement
Professional medical writing and editorial assistance was provided by Lauren Gallagher, R.Ph., Ph.D., of Peloton Advantage, LLC, an OPEN Health company, and funded by Takeda.
Legal entity responsible for the study
Takeda Pharmaceutical Company Limited.
Funding
Takeda Pharmaceutical Company Limited.
Disclosure
K. Muro: Other, Personal, Other, Consulting/advisory role, honoraria: Chugai Pharma, Ono Pharmaceutical; Other, Personal, Other, Consulting/advisory role: AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, MSD, Daiichi Sankyo, Shionogi, Kyowa Kirin, Gilead Sciences, Merck Serono, Pfizer, Sanofi, PAREXEL, Mediscience Planning, Sumitomo Dainippon Pharma, Solasia Pharma; Financial Interests, Personal, Other, Honoraria: Takeda, Lilly, Bayer, Sanofi, BMS; Financial Interests, Personal, Other, Honoraria, research grant: Taiho Pharmaceutical; Financial Interests, Personal, Research Grant: Astellas Pharma, Amgen Astellas Biopharma. J. Watanabe: Other, Personal, Invited Speaker: Covidien Japan, Johnson & Johnson/Janssen, Lilly Japan; Financial Interests, Institutional, Research Grant: Medtronic, TERUMO. K. Shitara: Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb, Takeda; Financial Interests, Personal, Other, Consulting/advisory role: Lilly, BMS, Takeda, Pfizer, Ono Pharmaceutical, MSD, Taiho, Novartis, Abbvie, GSK, Daiichi Sankyo, Boehringer Ingelheim, Janssen; Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Taiho, Chugai Pharma, Ono Pharmaceutical, Astellas Pharma, Medi Science, Eisai, Amgen. K. Yamazaki: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol-Myers Squibb ; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. E. Oki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Lilly Japan, Takeda, Ono Pharmaceutical, Bayer Yakuhin, Bristol-Myers Squibb Japan. T. Sato: Other, Personal, Other, Consulting/advisory role: Takeda; Other, Personal, Invited Speaker: Chugai Pharma, Lilly Japan, Taiho Oncology, Takeda, Bayer Yakuhin, Ono Yakuhin, Daiichi Sankyo/UCB Japan. T. Naitoh: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Taiho Pharmaceutical, Kaken, Daiichi Sankyo, Eli Lilly Japan, Takeda, Merck, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Chugai Pharma, Taiho Pharmaceutical, Kaken, Daiichi Sankyo, Eli Lilly Japan. Y. Komatsu: Other, Personal, Invited Speaker: Ono, Taiho, Chugai, Eli Lilly, Bayer Yakuhin; Financial Interests, Personal, Research Grant: Ono, Taiho, Daiichi Sankyo, Chugai, IQVIA. T. Kato: Financial Interests, Personal, Other, Honoraria: Chugai, Yakult Honsha, Ono Pharmaceutical, Takeda, Lilly Japan, Taiho Pharmaceutical, Asahi Kasei; Financial Interests, Personal, Research Grant: Chugai. M. Hihara: Financial Interests, Personal, Full or part-time Employment: Takeda. J. Soeda: Financial Interests, Personal, Full or part-time Employment: Takeda. K. Yamamoto: Financial Interests, Personal, Other, Honoraria: Chugai, J-Pharma, Johokiko, Triceps, CMIC Holdings; Financial Interests, Personal, Research Grant: Taiho, Boehringer Ingelheim, Takeda, Daiichi-Sankyo, Astellas. H. Uetake: Other, Personal, Invited Speaker: Takeda, Chugai, Taiho. K. Tsuchihara: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Novartis, Takeda, Miyarisan Pharmaceutical, BMS Japan, AstraZeneca. T. Yoshino: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical, MSD; Financial Interests, Institutional, Research Grant: MSD, Daiichi Sankyo, Ono Pharmaceutical, Taiho Pharmaceutical, Amgen, Sanofi, Pfizer, Genomedia Inc., Sysmex, Nippon Boehringer Ingelheim, Chugai Pharma. All other authors have declared no conflicts of interest.