Martina Makrutzki
Hoffmann-La Roche
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Featured researches published by Martina Makrutzki.
Lancet Oncology | 2012
Aimery de Gramont; Eric Van Cutsem; Hans-Joachim Schmoll; Josep Tabernero; Stephen Clarke; Malcolm J. Moore; David Cunningham; Thomas H. Cartwright; J. Randolph Hecht; F. Rivera; Seock-Ah Im; G. Bodoky; Ramon Salazar; F. Maindrault-Goebel; Einat Shacham-Shmueli; Emilio Bajetta; Martina Makrutzki; A. Shang; Thierry André; Paulo M. Hoff
BACKGROUND Bevacizumab improves the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer. Our aim was to assess the use of bevacizumab in combination with oxaliplatin-based chemotherapy in the adjuvant treatment of patients with resected stage III or high-risk stage II colon carcinoma. METHODS Patients from 330 centres in 34 countries were enrolled into this phase 3, open-label randomised trial. Patients with curatively resected stage III or high-risk stage II colon carcinoma were randomly assigned (1:1:1) to receive FOLFOX4 (oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), and fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 1; leucovorin 200 mg/m(2) plus fluorouracil 400 mg/m(2) bolus plus 600 mg/m(2) 22-h continuous infusion on day 2) every 2 weeks for 12 cycles; bevacizumab 5 mg/kg plus FOLFOX4 (every 2 weeks for 12 cycles) followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks); or bevacizumab 7·5 mg/kg plus XELOX (oxaliplatin 130 mg/m(2) on day 1 every 2 weeks plus oral capecitabine 1000 mg/m(2) twice daily on days 1-15) every 3 weeks for eight cycles followed by bevacizumab monotherapy 7·5 mg/kg every 3 weeks (eight cycles over 24 weeks). Block randomisation was done with a central interactive computerised system, stratified by geographic region and disease stage. Surgery with curative intent occurred 4-8 weeks before randomisation. The primary endpoint was disease-free survival, analysed for all randomised patients with stage III disease. This study is registered with ClinicalTrials.gov, number NCT00112918. FINDINGS Of the total intention-to-treat population (n=3451), 2867 patients had stage III disease, of whom 955 were randomly assigned to receive FOLFOX4, 960 to receive bevacizumab-FOLFOX4, and 952 to receive bevacizumab-XELOX. After a median follow-up of 48 months (range 0-66 months), 237 patients (25%) in the FOLFOX4 group, 280 (29%) in the bevacizumab-FOLFOX4 group, and 253 (27%) in the bevacizumab-XELOX group had relapsed, developed a new colon cancer, or died. The disease-free survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1·17 (95% CI 0·98-1·39; p=0·07), and for bevacizumab-XELOX versus FOLFOX4 was 1·07 (0·90-1·28; p=0·44). After a minimum follow-up of 60 months, the overall survival hazard ratio for bevacizumab-FOLFOX4 versus FOLFOX4 was 1·27 (1·03-1·57; p=0·02), and for bevacizumab-XELOX versus FOLFOX4 was 1·15 (0·93-1·42; p=0·21). The 573 patients with high-risk stage II cancer were included in the safety analysis. The most common grade 3-5 adverse events were neutropenia (FOLFOX4: 477 [42%] of 1126 patients, bevacizumab-FOLFOX4: 416 [36%] of 1145 patients, and bevacizumab-XELOX: 74 [7%] of 1135 patients), diarrhoea (110 [10%], 135 [12%], and 181 [16%], respectively), and hypertension (12 [1%], 122 [11%], and 116 [10%], respectively). Serious adverse events were more common in the bevacizumab groups (bevacizumab-FOLFOX4: 297 [26%]; bevacizumab-XELOX: 284 [25%]) than in the FOLFOX4 group (226 [20%]). Treatment-related deaths were reported in one patient receiving FOLFOX4, two receiving bevacizumab-FOLFOX4, and five receiving bevacizumab-XELOX. INTERPRETATION Bevacizumab does not prolong disease-free survival when added to adjuvant chemotherapy in resected stage III colon cancer. Overall survival data suggest a potential detrimental effect with bevacizumab plus oxaliplatin-based adjuvant therapy in these patients. On the basis of these and other data, we do not recommend the use of bevacizumab in the adjuvant treatment of patients with curatively resected stage III colon cancer. FUNDING Genentech, Roche, and Chugai.
Annals of Oncology | 2013
Stefan Kubicka; Richard Greil; T. André; J. Bennouna; J. Sastre; E. Van Cutsem; R. von Moos; Pia Österlund; Irmarie Reyes-Rivera; T. Müller; Martina Makrutzki; D. Arnold; Agmt groups
BACKGROUND ML18147 evaluated continued bevacizumab with second-line chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard first-line bevacizumab-containing therapy. PATIENTS AND METHODS Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutation-specific Scorpion amplification-refractory mutation system). No adjustment was made for multiplicity; analyses were not powered to detect statistically significant differences. RESULTS Of 820 patients, 616 (75%) had unambiguous KRAS data; 316 (51%) had KRAS wild-type tumors and 300 (49%) had mutant KRAS tumors. The median progression-free survival (PFS) was 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P < 0.0001; HR = 0.61; 95% confidence interval (CI): 0.49-0.77] for wild-type KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.56-0.89) for mutant KRAS. The median overall survival (OS) was 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.53-0.90) for wild-type KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.71-1.18) for mutant KRAS. In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266). CONCLUSIONS Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.
JAMA Oncology | 2017
Eli L. Diamond; Vivek Subbiah; A. Craig Lockhart; Jean Yves Blay; Igor Puzanov; Ian Chau; Noopur Raje; Jürgen Wolf; Joseph P. Erinjeri; Jean Torrisi; Mario E. Lacouture; Elena Elez; Ferran Martínez-Valle; Benjamin Durham; Maria E. Arcila; Gary A. Ulaner; Omar Abdel-Wahab; Bethany Pitcher; Martina Makrutzki; Todd Riehl; J. Baselga; David M. Hyman
Importance The histiocytic neoplasms Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are highly enriched for BRAF V600 mutations and have been previously shown to be responsive to treatment with vemurafenib, an inhibitor of the BRAF V600 kinase. However, the long-term efficacy and safety of prolonged vemurafenib use in these patients are not defined. Here we analyze the final efficacy and safety data for vemurafenib in patients with ECD and LCH enrolled in the VE-BASKET study. Objective To determine the efficacy and safety of vemurafenib in adults with ECD or LCH enrolled in the VE-BASKET study. Design, Setting, and Participants The VE-BASKET study was an open-label, nonrandomized, multicohort study for patients with nonmelanoma cancers harboring the BRAF V600 mutation. Patients with BRAF V600–mutant ECD or LCH were enrolled in an “other solid tumor” cohort of the VE-BASKET study, and they were enrolled in the present study. Interventions Patients received vemurafenib, 960 mg, twice daily continuously until disease progression, study withdrawal, or occurrence of intolerable adverse effects. Main Outcomes and Measures The primary end point was confirmed objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Secondary end points included progression-free survival (PFS), overall survival (OS), metabolic response by modified positron-emission tomography (PET) Response Criteria in Solid Tumors (PERCIST) using 18F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT), and safety. Results A total of 26 patients from the VE-BASKET trial (22 with ECD, 4 with LCH) were included in the present study (14 women and 12 men; median age, 61 years; age range, 51-74 years). The confirmed ORR was 61.5% (95% CI, 40.6%-79.8%) in the overall cohort and 54.5% (95% CI, 32.2%-75.6%) in patients with ECD. All evaluable patients achieved stable disease or better. The median PFS and OS had not been reached in the overall cohort at study closure despite a median follow-up of 28.8 months; 2-year PFS was 86% (95% CI, 72%-100%), and 2-year OS was 96% (95% CI, 87%-100%). All 15 patients evaluated by FDG-PET/CT achieved a metabolic response, including 12 patients (80%) with a complete metabolic response. The most common adverse events (AEs) in the overall cohort included arthralgia, maculopapular rash, fatigue, alopecia, prolonged QT interval, skin papilloma, and hyperkeratosis. Hypertension and dermatologic AEs occurred at higher rates than those reported in metastatic melanoma. Conclusions and Relevance In this study, vemurafenib had prolonged efficacy in patients with BRAF V600–mutant ECD and LCH and warrants consideration as a new standard of care for these patients.
Journal of Clinical Oncology | 2018
Thomas Kaley; Mehdi Touat; Vivek Subbiah; Antoine Hollebecque; Jordi Rodon; A. Craig Lockhart; Vicki L. Keedy; Franck Bielle; Ralf-Dieter Hofheinz; Florence Joly; Jean-Yves Blay; Ian Chau; Igor Puzanov; Noopur Raje; Jürgen Wolf; Lisa M. DeAngelis; Martina Makrutzki; Todd Riehl; Bethany Pitcher; José Baselga; David M. Hyman
Purpose BRAFV600 mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma. We sought to determine the activity of vemurafenib, a selective inhibitor of BRAFV600, in patients with gliomas that harbor this mutation. Patients and Methods The VE-BASKET study was an open-label, nonrandomized, multicohort study for BRAFV600-mutant nonmelanoma cancers. Patients with BRAFV600-mutant glioma received vemurafenib 960 mg twice per day continuously until disease progression, withdrawal, or intolerable adverse effects. Key end points included confirmed objective response rate by RECIST version 1.1, progression-free survival, overall survival, and safety. Results Twenty-four patients (median age, 32 years; 18 female and six male patients) with glioma, including malignant diffuse glioma (n = 11; six glioblastoma and five anaplastic astrocytoma), PXA (n = 7), anaplastic ganglioglioma (n = 3), pilocytic astrocytoma (n = 2), and high-grade glioma, not otherwise specified (n = 1), were treated. Confirmed objective response rate was 25% (95% CI, 10% to 47%) and median progression-free survival was 5.5 months (95% CI, 3.7 to 9.6 months). In malignant diffuse glioma, best response included one partial response and five patients with stable disease, two of whom had disease stabilization that lasted more than 1 year. In PXA, best response included one complete response, two partial responses, and three patients with stable disease. Additional partial responses were observed in patients with pilocytic astrocytoma and anaplastic ganglioglioma (one each). The safety profile of vemurafenib was generally consistent with that of previously published studies. Conclusion Vemurafenib demonstrated evidence of durable antitumor activity in some patients with BRAFV600-mutant gliomas, although efficacy seemed to vary qualitatively by histologic subtype. Additional study is needed to determine the optimal use of vemurafenib in patients with primary brain tumors and to identify the mechanisms driving differential responses across histologic subsets.
The New England Journal of Medicine | 2015
David M. Hyman; Igor Puzanov; Subbiah; Jason E. Faris; Ian Chau; Jean Yves Blay; Juergen Wolf; Noopur Raje; Eli L. Diamond; Antoine Hollebecque; Gervais R; Elez-Fernandez Me; Antoine Italiano; Ralf Hofheinz; Manuel Hidalgo; Emily Chan; Martin Schuler; Lasserre Sf; Martina Makrutzki; Sirzen F; Veronese Ml; Tabernero J; José Baselga
Journal of Clinical Oncology | 2011
A. de Gramont; E. Van Cutsem; Josep Tabernero; Malcolm J. Moore; David Cunningham; F. Rivera; Seock-Ah Im; Martina Makrutzki; A. Shang; Paulo M. Hoff
Annals of Oncology | 2016
Grant A. McArthur; Michele Maio; Ana Arance; Paul Nathan; Christian U. Blank; M.-F. Avril; Claus Garbe; Axel Hauschild; Dirk Schadendorf; Omid Hamid; Michael Fluck; M. Thebeau; Jacob Schachter; Richard F. Kefford; M. Chamberlain; Martina Makrutzki; S. Robson; Rene Gonzalez; Kim Margolin
Journal of Clinical Oncology | 2011
T. André; E. Van Cutsem; H.-J. Schmoll; Josep Tabernero; Stephen Clarke; Malcolm J. Moore; David Cunningham; Thomas H. Cartwright; Joel Randolph Hecht; F. Rivera; Seock-Ah Im; G. Bodoky; Ramon Salazar; F. Maindrault-Goebel; Einat Shacham Shmueli; Emilio Bajetta; Martina Makrutzki; A. Shang; A. de Gramont; Paulo M. Hoff
European Journal of Cancer | 2017
Christian U. Blank; James Larkin; Ana Arance; Axel Hauschild; Paola Queirolo; Michele Del Vecchio; Paolo Antonio Ascierto; Ivana Krajsova; Jacob Schachter; Bart Neyns; Claus Garbe; Vanna Chiarion Sileni; Mario Mandalà; Helen Gogas; Enrique Espinosa; Geke A.P. Hospers; Wilson H. Miller; Susan Robson; Martina Makrutzki; Vladan Antic; Michael P. Brown
Journal of Clinical Oncology | 2017
Vivek Subbiah; Radj Gervais; Gregory J. Riely; Antoine Hollebecque; Jean-Yves Blay; Enriqueta Felip; Martin Schuler; Anthony Gonçalves; Antoine Italiano; Vicki L. Keedy; Ian Chau; Igor Puzanov; Noopur Raje; Martina Makrutzki; Todd Riehl; Bethany Pitcher; David M. Hyman; José Baselga