Choice of posters dealing with Cetuximab, M7824 & Trifluridine/Tipiracil

Sebastian Stintzing, et al.

Cost-effectiveness of FOLFIRI + cetuximab vs FOLFIRI + bevacizumab in the first-line (1L) treatment of RAS wild-type (wt) metastatic colorectal cancer (mCRC) in Germany: Data from the FIRE-3 (AIO KRK-0306) study.

Conclusions: Based on our analyses, FOLFIRI + cetuximab is cost-effective compared with FOLFIRI + bevacizumab in patients in Germany with RAS wt mCRC at official WTP thresholds applied by relevant European health technology assessment agencies. The cost-effectiveness of FOLFIRI + cetuximab is more pronounced in the subgroup of patients with RAS wt, LS tumors.

J Clin Oncol 36, 2018 (suppl 4S; abstr 800)

 


Sang-A Kim, et al.

Liver and/or lung metastasectomy after cetuximab or bevacizumab+FOLFIRI chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC).

Conclusions: A substantial proportion of patients, especially those with metastatic lesions less than 8, could receive CS after cetuximab or bevacizumab+FOLFIRI chemotherapy. Among the patients with R0 resection, a certain proportion of patients could achieve long-term DFS after CS. CET tended to show higher rate of CS. However, the median DFS after R0 resection was not significantly different between the two groups

J Clin Oncol 36, 2018 (suppl 4S; abstr 843)


Timothy Jay Price, et al.

Impact of primary tumor side (TS) on outcomes of once-every-2-weeks (q2w) cetuximab + first-line (1L) FOLFOX or FOLFIRI in patients with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the phase 2 APEC trial.

Conclusions: 

The tumor side subgroup analysis of the phase 2 APEC study confirms the utility of cetuximab + chemotherapy as a standard-of-care treatment option for patients with left-sided, RAS wt mCRC

– Chemotherapy backbone did not appear to significantly affect outcomes for patients with left-sided, RAS wt tumors, and both cetuximab + FOLFIRI and cetuximab + FOLFOX yielded a median OS of >30 months for these patients, in agreement with observations made in pivotal phase 3 studies4-6

Additionally, 1L cetuximab q2w in combination with either chemotherapy backbone yielded ORRs of ≥50.0% in patients with right-sided tumors (and indeed, resection rates were similar between the overall left- and right-sided populations), providing support for cetuximab-based regimens as viable options for right-sided mCRC when patients require rapid tumor shrinkage to improve or prevent symptoms or facilitate resection

– Interestingly, better PFS and OS outcomes for patients with right-sided, RAS wt tumors were suggested with FOLFIRI (median OS >30 months in this subgroup) as compared with FOLFOX

§ Although the rate of BRAF mutations in the cetuximab + FOLFOX and cetuximab + FOLFIRI cohorts may partially explain dissimilarities in PFS and OS, another possible reason for the observed trend may be related to synergy between cetuximab and irinotecan, as previously documented in preclinical models

– These results should be interpreted with caution due to the low number of patients with right-sided mCRC, but can serve to generate interesting hypotheses regarding the choice of chemotherapy backbone combined with 1L cetuximab for the treatment of patients with right-sided, RAS wt mCRC

The APEC study revealed no new or unexpected safety findings for 1L cetuximab q2w + chemotherapy

– No safety analysis was performed for this tumor side subgroup analysis because there is no existing evidence that the safety profile differs meaningfully between right- and left-sided mCRC

Clinical trial information: NCT00778830

J Clin Oncol 36, 2018 (suppl 4S; abstr 747)


Scott Kopetz, et al.

M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with heavily pretreated CRC: Preliminary results from a phase I trial.

Conclusions: M7842 is an innovative, first in class fusion protein designed to simultaneously target 2 immune suppressive pathways, TGF-Beta and PD-L1. Activity has previously been demonstrated in preclinical murine models and in a phase 1, 3+3 dose-escalation study. In this expansion cohort of heavily pre-treated patients with advanced CRC, 1 patient had durable PR, 1 had SD, and 27 had PD or BOR upon treatment with M7824.

- The patients with PR ongoing for 8.3 months had CRC that was MSS, CMS4, KRAS mutant, and PD-L1+

- A second patient who had initial progression at 5 months and was treated with palliative RT remains well at 13 months.

M7824 had a manageable safety profile in this patient population. Multiple expansion cohorts are currently ongoing in a range of tumor types.

An MD Anderson Cancer Center study in patients with CMS4 CRC is in preparation to further explore a potential signal in high-risk CRC patients.

Clinical trial information: NCT02517398

J Clin Oncol 36, 2018 (suppl 4S; abstr 764)


Takayuki Yoshino, et al.

TRUSTY: A randomized multicenter phase II/III study of trifluridine/tipiracil and bevacizumab versus irinotecan, fluoropyrimidine, and bevacizumab as second-line treatment in patients with metastatic colorectal cancer progressive during or following first-line oxaliplatin-based chemotherapy.

The primary endpoint is overall survival. The non-inferiority hypothesis will be achieved if the upper limit of the two-sided 95% CI of the HR is below 1.33 (as HR scale, power 0.80). If achieved, the non-inferiority hypothesis with the margin of 1.25 (as HR) and the superiority will be consequently tested. Secondary endpoints include progression-free survival, time to treatment failure, response rate, disease control rate, subsequent treatment, time to post-study treatment failure, the quality of life, and adverse events. The target sample size is 524 patients. Patients will be enrolled from October 2017. Clinical trial information: 173618.

J Clin Oncol 36, 2018 (suppl 4S; abstr TPS881)


Jacqueline N. Chu, et al.

Nivolumab versus nivolumab with ipilimumab versus trifluridine/tipiracil for metastatic microsatellite instability-high colorectal cancer: A modeling decision analysis.

Conclusions: Our modeling analysis finds that both single and dual checkpoint blockade yield significantly increased overall survival and QALYs for MSI-H mCRC compared to third-line chemotherapy, but were not cost-effective because of nivolumab cost. Decreases in drug pricing and/or duration of maintenance nivolumab could make nivolumab monotherapy cost-effective.

J Clin Oncol 36, 2018 (suppl 4S; abstr 829)


Robert J. Mayer, et al.

Safety of trifluridine/tipiracil (FTD/TPI) in elderly patients with metastatic colorectal cancer.

Conclusions: This analysis from the EAP showed that the safety profile and treatment duration of FTD/TPI in patients aged ≥65 with mCRC were similar to those in patients aged < 65. FTD/TPI is well tolerated and can be considered in patients aged ≥65 with mCRC. Clinical trial information: NCT-02286492.

J Clin Oncol 36, 2018 (suppl 4S; abstr 752)


Anuj K. Patel, et al

Comparison of the real-world adherence and compliance patterns with trifluridine/tipiracil (FTD/TPI) and regorafenib (REG) for the treatment of metastatic colorectal cancer (mCRC)

Conclusions: In this retrospective study of mCRC patients, patients on FTD/TPI were significantly more likely to adhere and comply with therapy compared to those on REG.

J Clin Oncol 36, 2018 (suppl 4S; abstr 666)


Takeshi Kawakami, et al.

Predictive value of tumor growth rate during previous treatment for tumor response to regorafenib (REGO) and trifluridine/tipiracil (TFTD) in metastatic colorectal cancer (mCRC).

Conclusions: TGR during the pre-treatment period would be helpful in selecting between REGO and TFTD, especially for pts with slow-growing tumors. Pts with appearance of new lesions may not benefit from either REGO or TFTD as salvage treatment.

J Clin Oncol 36, 2018 (suppl 4S; abstr 766)

 


Audrey E. Kam, et al.

Clinical outcome and prognosis of metastatic colorectal cancer (mCRC) patients (pts) on phase 1 trials: A single institution experience from 1999 to 2016.

Conclusions: Patients with mCRC enrolled on phase 1 trials had a CBR of 33.2% and median OS of 8.2 mos, which exceeds third line therapies including regorafenib and trifluridine/tipiracil. Negative prognostic factors for OS were: age > 60, albumin < 3.5, direct bilirubin > ULN, and WBC > 5.2. A risk score based on these parameters showed that patients with a higher score had a significantly shorter OS, which may be useful in selecting patients for phase 1 trials.

J Clin Oncol 36, 2018 (suppl 4S; abstr 828)