Startseite
Kongressberichte 2019
Annual Meeting of the American Society of Clinical Oncology 2019
Colon Cancer
Poster Presentations
Choice of Poster Presentations
Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, et al
Conclusions: The combination of regorafenib 80mg plus nivolumab had a manageable safety profiles and encouraging anti-tumor activity in MSS GC and CRC pts, which warrants further investigations in a larger cohort. Updated biomarker analysis will be presented. Clinical trial information: NCT03406871
Brendan John Guercio, Alan P. Venook, Sui Zhang, Fang-Shu Ou, et al.
Conclusions: In patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with reduced risk of disease progression and mortality. These data suggest that energy-balance associated biomarkers may offer prognostic and biologic insights into mCRC. Support: U10CA180821, U10CA180882, BMS, Genentech, Pfizer, Sanofi; https://acknowledgments.alliancefound.org.
Ke-Feng Ding, Qian Xiao, Xiangxing Kong, Yeting Hu, et al.
Conclusions: This study is the first effort to characterize circulating bacteria DNA in patients with ADC and ADM. Our findings revealed significant difference in relative abundance of several bacterial species between ADC, ADM and HC. A predictive model constructed with selected microbial features accurately distinguished ADC and ADM from HC. Circulating bacteria biomarkers represent potential non-invasive tools for early diagnosis of colorectal neoplasia.
Filippo Pietrantonio, Riccardo Lobefaro, Maria Antista, Rosalba Miceli, et al.
Conclusions: The use of TMZ should be explored by phase 3 trials enrolling MGMT IHC-negative +/- high MGMT % methylated mCRC.Clinical trial information: NCT02414009
Zhen Zhang, Xinchen Sun, Anwen Liu, Yuan Zhu, et al.
Conclusions: Adding irinotecan guided by UGT1A1 to capecitabine-based neoadjuvant chemoradiotherapy significantly increases complete tumor response. The treatment toxicities were increased but tolerable. This treatment can be as an option for ‘watch and wait’ approach. Clinical trial information: NCT02605265
Michael Geissler, Jorge Riera-Knorrenschild, Uwe Marc Martens, Swantje Held, et al.
Conclusions: The addition of Pmab to a mFOLFOXIRI regimen in patients with RASwildtype metastatic colorectal cancer significantly improved objective response rate and the rate of secondary resection of metastases. Although PFS was comparable, there was a strong trend towards improved OS in the Pmab arm. Future studies are warranted to confirm this trend towards improved overall survival with this regimen. Clinical trial information: NCT01328171
Heinz-Josef Lenz, Sara Lonardi, Vittorina Zagonel, Eric Van Cutsem, et al.
Conclusions: NIVO + low-dose IPI demonstrated robust and durable clinical benefit and was well tolerated. Evaluated subgroups had responses consistent with the overall population. NIVO + low-dose IPI may represent a new 1L treatment option for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188
| NIVO + low-dose IPI n/N (%) |
||||
|---|---|---|---|---|
| ORR (all patients)c | 27/45 (60) | |||
| Age, years | <65 | ≥65 | 14/22 (64) | 13/23 (57) |
| ECOG performance status | 0 | ≥1 | 13/25 (52) | 14/20 (70) |
| Prior adjuvant/neoadjuvant therapy | Yes | No | 12/19 (63) | 15/26 (58) |
| Mutation status | ||||
| BRAF/KRAS wild type | 8/13 (62) | |||
| BRAF mutationc | 12/17 (71) | |||
| KRAS mutation | 5/10 (50) | |||
| Unknown | 2/5 (40) | |||
aInvestigator assessed. bMedian follow-up defined as time on study from first dose to data cutoff, which was 13.8 months (range 9–19). cPreviously reported.
Mohamad Bassam Sonbol, Luke Mountjoy, Belal Firwana, Diana Almader-Douglas, et al.
Conclusions: A maintenance strategy with at least a FP with or without the addition of bevacizumab is preferred. However, given the lack of a clear OS benefit, obs is an acceptable alternative. Optimal maintenance strategies should be dependent on factors including patient preferences, cost and toxicities.
| Strategy | SUCRA % for OS | SUCRA % for PFS |
|---|---|---|
| Obs | 0.3 | 0.3 |
| Bev | 32.6 | 36.5 |
| FP | 81.3 | 67.1 |
| FP + Bev | 73.2 | 99.8 |
| CTX | 46 | 46.3 |
Tony R. Reid, George A. Fisher
Conclusions: The results of this trial demonstrate improved efficacy and efficacy of RRx-001 + irinotecan compared with regorafenib in patients with metastatic colorectal cancer. Clinical trial information: NCT02096354
Volker Heinemann, Dominik Paul Modest, Ludwig Fischer von Weikersthal, Thomas Decker, et al.
Conclusions: In the overall RAS wt population, younger patients have a significant OS benefit when treated with FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab, while this was not the case in patients older than 70 years.
| ≤ 65 years | N | ORR (%) |
p* | PFS (months) |
p# (HR) |
OS (months) |
P# (HR) |
|---|---|---|---|---|---|---|---|
| FOLFIRI + Cet | 104 | 75.6 | 0.08 | 11.2 | 0.42 1.10 |
33.1 | 0.01 0.68 |
| FOLFIRI + Bev | 105 | 63.0 | 10.2 | 24.8 | |||
| ≤ 70 years | N | ORR (%) |
P* | PFS (months) |
P# (HR) |
OS (months) |
P# (HR) |
| FOLFIRI + Cet | 136 | 79.1 | 0.02 | 10.7 | 0.52 1.10 |
33.3 | 0.02 0.73 |
| FOLFIRI + Bev | 150 | 65.2 | 10.5 | 27.5 | |||
| > 70 years | N | ORR (%) |
p* | PFS (months) |
p# (HR) |
OS (months) |
P# (HR) |
| FOLFIRI + Cet | 63 | 72.7 | 0.28 | 8.8 | 0.90 | 23.6 | 0.25 |
| FOLFIRI + Bev | 51 | 61.9 | 10.4 | 0.98 | 23.8 | 0.67 |
*= Fisher`s exact test p; #= Logrank Test p
Eiji Oki, Akitaka Makiyama, Yuji Miyamoto, Masahito Kotaka, et al.
Conclusions: The combination of trifluridine/tipiracil plus bevacizumab is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer. Hematological adverse events were need for caution. The primary endpoint of PFS will be presented in the end of this year. Clinical trial information: UMIN000025241.
Enrique Aranda, Pilar Garcia-Alfonso, Jose María Vieitez, Maria Jose Ortiz, et a.
Conclusions: In the low risk mCRC pts according to bCTCs, BRAFand/or PIK3CA MUT have a negative impact in OS and a trend to worse PFS in the ITT population. The impact of treatment is under evaluation and will be provided during the meeting. Clinical trial information: 2012-000840-90.
| ITT population N=240 |
FOLFIRI + Bev N=126 |
FOLFIRI + Cet N=114 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| WT N=196 |
MUT N=44 |
HR (IC95%) p value |
WT N=102 |
MUT N=24 |
All | HR (IC95%) p value |
WT N=94 |
MUT N=20 |
All | HR (IC95%) p value |
|
| PFS m | 12.7 | 9.1 | 1.136 (0.739-1.745) p=0.562 | 12.9 | 9.3 | 12.5 | 0.992 (0.554-1.776) p=0.978 | 12.5 | 8.5 | 11,5 | 1.452 (0.765-2.755) p=0.253 |
| OS m | 34,7 | 20,7 | 1.878 (1.269-2.779) p=0.0016 | 36.0 | 18.6 | 32,9 | 2.022 (1.194-3.425) p=0.008 | 34.1 | 23.7 | 33.3 | 1.714 (0.947-3.102) p=0.078 |
Maria Alessandra Calegari, Ina Valeria Zurlo, Michele Basso, Armando Orlandi, et al.
Conclusions: Our analysis, although underpowered, generates the hypothesis of a superiority of CTr/r in comparison to REG or TAS-102, in both efficacy and activity. Given the retrospective nature of our analysis, and the potential role of selection bias in treatment assignment, a prospective validation is mandatory.
Stefan Kasper, Gerrit zur Hausen, Alexander Stein, Sebastian Stintzing, et al.
Methods: This is an interventional, randomized, open label, multicenter, phase IIb study in patients with advanced mCRC. Eligible patients will be randomized 1:1 and receive either ramucirumab and TAS102 (ramucirumab 8 mg/kg on d1+15, q4w and TAS102 35 mg/m² on d1-5 and d8-12, q4w) or TAS102 alone. Primary endpoint is overall survival as assessed by the Kaplan-Meier method, assuming a 6 months survival probability of 70% with ramucirumab in combination with TAS102 and 58% with TAS102 alone. Treatment groups are compared using the log-rank test. A total of 144 patients will be enrolled at 30 sites (1-sided alpha 0.10, power 0.80). Main secondary endpoints are overall response rate, disease control rate, progression free survival and quality of life. In addition, a large comprehensive translational research program will be conducted to identify novel predictive and prognostic biomarkers. The study started in December 2018. By February 2019, a total of 3 patients have been enrolled. Clinical trial information: NCT03520946
Ramon Salazar, Alfredo Carrato, Teresa Garcia Garcia, Javier Gallego Plazas, et al.
Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021
Toshiki Masuishi, Toshikazu Moriwaki, Shota Fukuoka, Atsuo Takashima, et al.
Conclusions: Our predictive model for early mortality after initiation of REG or FTD/TPI might be useful for selecting pts who should not receive either these drugs.
Conclusions: While ctDNA testing may not be ready for primetime in all advanced cancers, it is increasingly being adopted in practice for especially metastatic CRC. Of particular value is the serial ctDNA testing in the RAS/RAF wildtype subset and now BRAF V600E mutant CRC on anti-EGFR based therapies.
| Total number of patients | 322 |
|---|---|
| Total number of tests | 607 |
| Number of serial analyses | 127 |
| RAS/RAF wild-type | 214 (66.4%) |
| Number of RAS mutations | 83 (25.8%) |
| Number of V600E BRAF mutations | 18 (5.6%) |
| Number of non-V600EBRAF mutations | 7 (2.2%) |
| Number of HER2 amplifications | 13 (4%) |
| Number of HER2 mutations | 7 (2.2%) |
| MSI-High* | 3 (1%) |
*Of note, 25(7.8%) of CRC were dMMR/MSI-High in the cohort. CtDNA testing company started reporting MSI-High later in 3rd quarter of 2018.
Alberto F. Sobrero, Heinz-Josef Lenz, Cathy Eng, Werner Scheithauer, et al.
Conclusions: Post-study cetuximab was associated with improved OS in both treatment arms compared with post-study therapy without cetuximab and no subsequent therapy, suggesting that cetuximab-based therapy may be suitable as a standard treatment for pts with RAS wt mCRC in the rechallenge setting. Study limitations include a potential bias due to the differences in proportion of subsequent therapies with and without cetuximab between arms (almost 50% of pts in the irinotecan arm received post-study cetuximab) as well as the likelihood for pts who live longer to receive cetuximab in any subsequent therapy line.
| Subsequent therapy with cetuximab |
Subsequent therapy without cetuximab |
No subsequent therapy |
Total | |
|---|---|---|---|---|
| Cetuximab + irinotecan | ||||
| n | 26 | 98 | 107 | 231 |
| mOS (95% CI), mo | 28.0 (26.55-NE) | 13.8 (12.16-17.12) | 8.2 (6.51-11.76) | 12.3 (11.37-14.09) |
| Irinotecan | ||||
| n | 104 | 37 | 80 | 221 |
| mOS (95% CI), mo | 19.1 (13.21-21.45) | 9.5 (8.18-17.91) | 3.9 (3.12-5.88) | 12.0 (9.36-14.92) |
NE, not estimable.
Arndt Stahler, Sebastian Stintzing, Dominik Paul Modest, Ivan Jelas, et al.