Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
International Journal of Clinical Oncology
Erschienen in: International Journal of Clinical Oncology 11/2019

09.07.2019 | Original Article

Analysis of response-related endpoints in trials of first-line medical treatment of metastatic colorectal cancer

verfasst von: Giuseppe A. Colloca, Antonella Venturino, Domenico Guarneri

Erschienen in: International Journal of Clinical Oncology | Ausgabe 11/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Tumor radiologic response after systemic chemotherapy has been used as endpoint of trials of patients with metastatic colorectal cancer (mCRC), which can report the best overall response rate (ORR) and the disease control rate (DCR) by RECIST criteria as well as the early tumor shrinkage (ETS). The present study perform a trial-level analysis to verify whether such response-related endpoints are predictive of overall survival (OS).

Methods

After a systematic search, randomized clinical trials (RCTs) were selected each time they evaluated the three response endpoints and progression-free survival (PFS). Two arms per trial were selected, and the correlation between the difference in each endpoint and the difference in OS was calculated. The analysis then evaluated the effects of treatment on ∆ORR, or ∆DCR, ∆ETS, ∆PFS, and on ∆OS, using separate linear regressions for each of them, and the proportion of variability explained (R2trial) on OS for each of the four endpoints was calculated.

Results

The systematic review of the literature led to the selection of 12 RCTs, 7 phase-3 and 5 phase-2. ETS reported a different performance in the entire sample compared to phase-3 trials (R2trial = 0.172 vs. 0.842), differently from DCR (R2trial = 0.541 vs. 0.816) and ORR (R2trial = 0.349 vs. 0.740). Surprisingly, PFS predicted OS with a weak correlation, which was not significant in the subgroup of phase-3 studies (R2trial = 0.455 vs. 0.466).

Conclusion

The results of the present trial-level analysis report a good performance of two response-related endpoints, DCR and ETS, and suggest that they could be differently used depending on the setting of disease and the type of medical treatment.
Literatur
1.
Malvezzi M, Carioli G, Bertuccio P et al (2018) European cancer mortality predictions for the year 2018 with focus on colorectal cancer. Ann Oncol 29:1016–1022CrossRef
2.
Siegel R, Ma J, Zou Z et al (2014) Cancer statistics, 2014. CA Cancer J Clin 64:9–29CrossRef
3.
Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216CrossRef
4.
Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRef
5.
Colloca G, Venturino A, Guarneri D (2016) Analysis of clinical end points of randomised trials including bevacizumab and chemotherapy versus chemotherapy as first-line treatment of metastatic colorectal cancer. Clin Oncol 28(10):e155–e164CrossRef
6.
Choi H, Charnsangavej C, Faria SC et al (2007) Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 25(13):1753–1759CrossRef
7.
Chun YS, Vauthey JN, Boonsirikamchai P et al (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. J Am Med Assoc 302(21):2338–2344CrossRef
8.
Sakamaki K, Kito Y, Yamazaki K et al (2017) Exploration of time points and cut-off values for early tumor shrinkage to predict survival outcomes of patients with metastatic colorectal cancer treated with first-line chemotherapy using a biexponential model for change in tumour size. ESMO Open 2:e000275CrossRef
9.
Colloca GA, Venturino A, Guarneri D (2019) Early tumor shrinkage after first-line medical treatment of colorectal cancer: a meta-analysis. Int J Clin Oncol 24:231–240CrossRef
10.
Piessevaux H, Buyse M, Schlichting M et al (2013) Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 31:3764–3775CrossRef
11.
Van Cutsem E, Kohne C-H, Lang I et al (2011) Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 29:2011–2019CrossRef
12.
Douillard JY, Siena S, Cassidy J et al (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25:1346–1355CrossRef
13.
Douillard JY, Siena S, Peeters M et al (2015) Impact of early tumour shrinkage and resection on outcomes in patients with wild-type RAS metastatic colorectal cancer. Eur J Cancer 51:1231–1242CrossRef
14.
Fischer von Weikersthal L, Schalhorn A, Stauch M et al (2011) Phase III trial of irinotecan plus infusional 5-fluorouracil/folinic acid versus irinotecan plus oxaliplatin as first-line treatment of advanced colorectal cancer. Eur J Cancer 47:206–214CrossRef
15.
Giessen C, Laubender RP, Fischer von Weikersthal L et al (2013) Early tumor shrinkage in metastatic colorectal cancer: retrospective analysis from an irinotecan-based randomized first-line trial. Cancer Sci 104:718–724CrossRef
16.
Ye LC, Liu TS, Ren L et al (2013) Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol 31:1931–1938CrossRef
17.
Ye LC, Wei Y, Zhu DX et al (2015) Impact of early tumor shrinkage on clinical outcome in wild-type KRAS colorectal liver metastases treated with cetuximab. J Gastroenterol Hepatol 30:674–679CrossRef
18.
Heinemann V, Fischer von Weikersthal L, Decker T et al (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15:1065–1075CrossRef
19.
Stintzing S, Modest DP, von Fischer Weikersthal L et al (2014) Independent radiological evaluation of objective response, early tumor shrinkage, and depth of response in FIRE-3 (AIO KRK-0306) in the final RAS evaluable population. Ann Oncol 25(suppl 5):LBA11
20.
Loupakis F, Cremolini C, Masi G et al (2014) Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 371:1609–1618CrossRef
21.
Cremolini C, Loupakis F, Lonardi S et al (2014) Early tumor shrinkage (ETS) and deepness of response (DoR) to predict progression-free, postprogression, and overall survival: results from the phase III TRIBE trial. J Clin Oncol 32(suppl 3):521CrossRef
22.
Yamazaki K, Nagase M, Tamagawa H et al (2016) Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). Ann Oncol 27:1539–1546CrossRef
23.
Nagase M, Yamazaki K, Tamagawa H et al (2015) The impact of early tumor shrinkage on survival in WJOG4407G trial, a randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab in first-line treatment for metastatic colorectal cancer. J Clin Oncol 33(suppl 3):679CrossRef
24.
Bokemeyer C, Bondarenko I, Makhson A et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671CrossRef
25.
Moosmann N, Fischer von Weikersthal L, Vehling-Kaiser U et al (2011) Cetuximab plus capecitabine and irinotecan compared with cetuximab plus capecitabine and oxaliplatin as first-line treatment for patients with metastatic colorectal cancer: AIO KRK-0104—a randomized trial of the German AIO CRC study group. J Clin Oncol 29:1050–1058CrossRef
26.
Modest DP, Laubender RP, Stintzing S et al (2013) Early tumor shrinkage in patients with metastatic colorectal cancer receiving first-line treatment with cetuximab combined with either CAPIRI or CAPOX: an analysis of the German AIO KRK 0104 trial. Acta Oncol 52:956–962CrossRef
27.
Ducreux M, Adenis A, Pignon J-P et al (2013) Efficacy and safety of bevacizumab-based combination regimens in patients with previously untreated metastatic colorectal cancer: final results from a randomized phase II study of bevacizumab plus 5-fluorouracil, leucovorin plus irinotecan versus bevacizumab plus capecitabine plus irinotecan (FNCLCC ACCORD 13/0503 study). Eur J Cancer 49:1236–1245CrossRef
28.
Ichante J, Adenis A, Malka D et al (2011) Impact of early tumor shrinkage on long-term outcome in metastatic colorectal cancer (mCRC) treated with 5FU plus irinotecan plus leucovorin (FOLFIRI) or capecitabine plus irinotecan XELIRI plus bevacizumab. J Clin Oncol 29(suppl):e14041CrossRef
29.
Schwartzberg LS, Rivera F, Karthaus M et al (2014) PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorinm and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol 32:2240–2247CrossRef
30.
Rivera F, Karthaus M, Hecht JR et al (2017) Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma. Int J Colorectal Dis 32:1179–1190CrossRef
31.
Carrato A, Abad A, Massuti B et al (2017) First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: a randomised, phase II trial (PLANET-TTD). Eur J Cancer 81:191–202CrossRef
32.
Wolchock JD, Hoos A, O’Day S et al (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412–7420CrossRef
33.
Ciani O, Buyse M, Garside R et al (2015) Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer. J Clin Epidemiol 68(7):833–842CrossRef
34.
Lamarca A, Barriuso J, Kulke M et al (2018) Determination of an optimal response cut-off able to predict progression-free survival in patients with well-differentiated advanced pancreatic neuroendocrine tumours treated with sunitinib: an alternative to the current RECIST-defined response. Br J Cancer 118:181–188CrossRef
35.
Okuno M, Hatano E, Nishino H et al (2017) Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases? A systematic review. Eur J Surg Oncol 43(6):1003–1012CrossRef
36.
Primrose J, Falk S, Finch-Jones M et al (2014) Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial. Lancet Oncol 15(6):601–611CrossRef
37.
Masaki C, Sugino K, Saito N et al (2017) Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma. Endocrine J 64(8):819–826CrossRef
38.
Kim ST, Jang K-T, Lee SJ et al (2015) Tumor shrinkage at 6 weeks predicts favorable clinical outcomes in a phase III study of gemcitabine and oxaliplatin with or without erlotinib for advanced biliary tract cancer. BMC Cancer 15:530CrossRef
39.
Krajewski KM, Guo M, Van den Abbeele AD et al (2011) Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0; tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vasculare endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma. Eur Urol 59:562–586CrossRef
40.
Krajewski KM, Franketti Y, Nishino M et al (2014) 10% tumor diameter shrinkage on the first follow-up computed tomography predicts clinical outcome in patients with advanced renal cell carcinoma treated with angiogenesis inhibitors: a follow-up validation study. Oncologist 19:507–514CrossRef
41.
Modest DP, Stintzing S, Fischer von Weikersthal L et al (2017) Relation of early tumor shrinkage (ETS) observed in first-line treatment to efficacy parameters of subsequent treatment in FIRE-3 (AIOKRK0306). Int J Cancer 140(8):1918–1925CrossRef
42.
Taieb J, Rivera F, Siena S et al (2018) Exploratory analyses assessing the impact of early tumour shrinkage and depth of response on survival outcomes in patients with RAS wild-type metastatica colorectal cancer receiving treatment in three randomised panitumumab trials. J Cancer Res Clin Oncol 144(2):321–335CrossRef
43.
Heinemann V, Stintzing S, Modest DP et al (2015) Early tumour shrinkage (ETS) and depth of response (DpR) in the treatment of patients with metastatic colorectal cancer (mCRC). Eur J Cancer 51:1927–1936CrossRef
44.
Nakayama G, Gujii T, Murotani K et al (2016) Modified two-dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer. Cancer Sci 107:1492–1498CrossRef
45.
Fukada I, Araki K, Kobayashi K et al (2018) Pattern of tumor shrinkage during neoadjuvant chemotherapy is associated with prognosis in low-grade luminal early brast cancer. Radiology 286(1):49–57CrossRef
46.
Shindoh J, Loyer EM, Kopetz S et al (2012) Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol 30:4566–4572CrossRef
47.
Heinemann V, Rivera F, O’Neil BH et al (2016) A study-level meta-analysis of efficacy data from head-to-head first-line trials of epidermal growth factor receptor inhibitors versus bevacizumab in patients with RAS wild-type metastatic colorectal cancer. Eur J Cancer 67:11–20CrossRef
48.
Ito M, Kusaba H, Mukaide S et al (2017) Early tumor shrinkage indicates a favorable response to bevacizumab-based first-line chemotherapy for metastatic colorectal cancer. Anticancer Drugs 28(10):1166–1173CrossRef
49.
Qi W-X, Shen Z, Tang L-N et al (2014) Does the addition of targeted biological agents to first-line chemotherapy for advanced colorectal cancer increase complete response? A systematic review and meta-analysis. Colorectal Dis 16:O300–O307CrossRef
Metadaten
Titel
Analysis of response-related endpoints in trials of first-line medical treatment of metastatic colorectal cancer
verfasst von
Giuseppe A. Colloca
Antonella Venturino
Domenico Guarneri
Publikationsdatum
09.07.2019
Verlag
Springer Singapore
Erschienen in
International Journal of Clinical Oncology / Ausgabe 11/2019
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01504-z

Weitere Artikel der Ausgabe 11/2019

International Journal of Clinical Oncology 11/2019 Zur Ausgabe

Original Article

CDC20 and its downstream genes: potential prognosis factors of osteosarcoma

Original Article

Impact of oral voriconazole during chemotherapy for acute myeloid leukemia and myelodysplastic syndrome: a Japanese nationwide retrospective cohort study

Original Article

Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas

Original Article

Including positive lymph node count in the AJCC N staging may be a better predictor of the prognosis of NSCLC patients, especially stage III patients: a large population-based study

Original Article

Impact of pathological stage and histological subtype on clinical outcome of adjuvant chemotherapy of paclitaxel plus carboplatin versus oral uracil–tegafur for non-small cell lung cancer: subanalysis of SLCG0401 trial

Original Article

Efficacy of chemotherapy for older patients with gastric cancer: a multicenter retrospective cohort study

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise