Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM)

Hurwitz, Herbert I.; Tan, Benjamin; Reeves, James A.; Xiong, Henry Q.; Somer, Brad; Lenz, Heinz‐Josef; Hochster, Howard S.; Scappaticci, Frank A.; Palma, John F.; Price, Richard; Lee, John J.; Nicholas, Alan; Sommer, Nicolas; Bendell, Johanna C.

doi:10.1634/theoncologist.2018-0344

Cited by 64 publications

(43 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 6 The R0 resection rate in our study was low but similar in both study groups, although we did not look specifically at those with disease confined to the liver, a patient group that has previously been shown to benefit from FOLFOXIRI-bevacizumab. 5 16 …”

Section: Discussionmentioning

confidence: 99%

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

et al. 2020

View full text Add to dashboard Cite

Purpose5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab.Patients and methodsVISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS).ResultsThe intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively.ConclusionsFirst-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The R0 resection rate for the TRIBE trial was 15% [26]. The other 2 trials in the meta-analysis were the CHARTA which was published in an abstract form and the STEAM trial which reported liver resection rate of 17.2% [27,28] .…”

Section: Discussionmentioning

confidence: 99%

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer

Elshenawy

Badran

Aljubran

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. Patients and methods: Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of Capecitabine, oxaliplatin, Irinotecan, and Bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and two-monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy. Results: Fifty-three patients were enrolled. The median age was 52 years (range 23-74), 29(55%) were males, ECOG PS 0-1 was 13(66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22(42%) had a single metastatic site and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had higher incidence of males compared to non-surgical group ( 69.3% vs 47.2%,p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p=0.09), higher mutant Kras (53.8 % vs 34.2%, p=0.3) and higher response rate ( 84.6% vs 56.2%, p=0.3). With a median follow up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI); 9.1-20] and the median OS was 28.2 months (95% CI; 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI; 12.6-not reached) compared to 9.6 months (95% CI; 7.0-18.3) for the non-surgical group, Log-rank p =0.0165. The median OS for both groups was not reached (95% CI; 53.3-not reached) and 23.2 months (95% CI; 17.0-28.4) respectively, Log-rank p=0.0006). Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively. Conclusions: Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible. Trial registration: Clinicaltrials.gov, NCT01311050, registered March,06,2011, retrospectively registered. https://ClinicalTrials.gov/show/NCT01311050.

show abstract

Section: Discussionmentioning

confidence: 99%

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer

Elshenawy

Badran

Aljubran

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. Patients and methods: Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of Capecitabine, oxaliplatin, Irinotecan, and Bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and two-monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy. Results: Fifty-three patients were enrolled. The median age was 52 years (range 23-74), 29(55%) were males, ECOG PS 0-1 was 13(66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22(42%) had a single metastatic site and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had higher incidence of males compared to non-surgical group ( 69.3% vs 47.2%,p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p=0.09), higher mutant Kras (53.8 % vs 34.2%, p=0.3) and higher response rate ( 84.6% vs 56.2%, p=0.3). With a median follow up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI); 9.1-20] and the median OS was 28.2 months (95% CI; 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI; 12.6-not reached) compared to 9.6 months (95% CI; 7.0-18.3) for the non-surgical group, Log-rank p =0.0165. The median OS for both groups was not reached (95% CI; 53.3-not reached) and 23.2 months (95% CI; 17.0-28.4) respectively, Log-rank p=0.0006). Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively. Conclusions: Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible. Short title : Triplet chemotherapy regimens as conversion therapy for unresectable colorectal cancer Keywords: Colorectal cancer; Triplet chemotherapy; FOLFOXIRI-Bevacizumab; Surgery Trial registration: Clinicaltrials.gov, NCT01311050, registered March,06,2011, retrospectively registered. https://ClinicalTrials.gov/show/NCT01311050.

show abstract

Phase II Randomized Trial of Sequential or Concurrent FOLFOXIRI-Bevacizumab Versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM)

Cited by 64 publications

References 21 publications

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer

Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer

Contact Info

Product

Resources

About