Martin McCabe, PhD, on Ewing Sarcoma: Assessment of Topotecan, Cyclophosphamide, and High-Dose Ifosfamide

2022 ASCO Annual Meeting


Martin McCabe, PhD, of the University of Manchester, discusses a phase III assessment of chemotherapy for patients with recurrent and primary refractory Ewing sarcoma. The trial, called rEECur, is the first study to provide comparative toxicity and survival data for the four most commonly used chemotherapy regimens in this disease. The analysis showed that high-dose ifosfamide is more effective in prolonging survival than topotecan plus cyclophosphamide (Abstract LBA2).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The rEECur trial is the first randomized control trial of chemotherapy in relapsed and refractory Ewing sarcoma. Before we set up the study, there was obviously no randomized trials, there were very weak data from a series of small retrospective or early phase studies, but as a result, we had no standard of care and there was no defined consensus backbone for us to develop new trials of targeted therapies. We set up the rEECur trial as a multi-arm, multi-stage, simultaneous phase II, phase III randomized control trial of chemotherapy, and this is a very efficient way to study multiple regimens in a very rare patient population. We initially had four chemotherapy arms. We dropped the gemcitabine docetaxel arm in 2018 and the irinotecan-temozolomide arm in 2020, both on the basis of worse event-free survival and worse imaging response. The results are presented at ASCO 2022, with the phase III comparison between the two other arms, which are topotecan/cyclophosphamide and high-dose ifosfamide. The primary outcome was event-free survival, and there was a 2 month difference in median event, three survival between 3.5 months for topotecan/cyclophosphamide and 5.7 months for ifosfamide this equated to a 10% difference in 6-month survival, between 37% and 47%. The secondary outcome measure of overall survival also showed a benefit for ifosfamide, with a 5 month difference in median overall survival, with 10.5 months for topotecan/cyclophosphamide and 15.4 months for ifosfamide. Again, that equated to a 10% difference in both 1-year and 2-year survival, so 1-year survival was 45% versus 55%. We also noticed that there was an interaction between age and the treatment arms. So the benefits of ifosfamide were more obvious in children under 14 than in adolescence and adults. This was true, both for event-free and overall survival. For the secondary outcome of toxicity, the rate of neutropenic fever was similar between both the arms. The patients recruited to ifosfamide had a higher incidence of grade 3 infections, and they also had more renal toxicity and encephalopathy, which were toxicities that we expected, and they were present in 8% and 7% respectively. The other outcome measure that we looked at that we reported was quality of life. And although the quality of life differences were not significant, there was a trend towards improved quality of life in children receiving ifosfamide that wasn't present for children receiving topotecan/cyclophosphamide. There were no obvious trends in adults for quality of life. In conclusion, in the first randomized trial of chemotherapy, we've now shown that ifosfamide is more effective than topotecan/cyclophosphamide, and in turn, those arms are more effective than the two arms that were dropped earlier. However, the differences between these arms are quite subtle. What we actually need is new drugs and new combinations of therapies to cure more patients. Having said that, these data will be very important in us moving forward, both in terms of counseling patients and parents when they come to clinic about the best treatment, but also in designing trials for the future. The study remains open to the ifosfamide arm, and we've also introduced a carboplatin/etoposide arm, which is another chemotherapy regimen that we use in this setting, and we'll be introducing a TKI arm with lenvatinib in combination with ifosfamide later this year.

Related Videos

Breast Cancer

Nancy Davidson, MD: In It for the Long Haul: Outcomes in Hormone Receptor–Positive Breast Cancer

Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, reviews results from four abstracts about the importance of long-term follow-up in studies of adjuvant endocrine therapy for hormone receptor–positive breast cancer. Because the natural history of hormone receptor–positive breast cancer is long, an effort is underway to improve selection of patients by clinical parameters or biomarkers, refine the endocrine therapy background, and administer more effective combinations of endocrine therapy with other agents.

Neuroendocrine Tumors

Mairéad G. McNamara, PhD, MBBCh, on Neuroendocrine Carcinoma: Findings on Liposomal Irinotecan Plus Fluorouracil and Folinic Acid or Docetaxel

Mairéad G. McNamara, PhD, MBBCh, of The Christie NHS Foundation Trust, discusses phase II findings of the NET-02 trial, which explored an unmet need in the second-line treatment of patients with progressive, poorly differentiated extrapulmonary neuroendocrine carcinoma. In the trial, the combination of liposomal irinotecan, fluorouracil, and folinic acid, but not docetaxel, met the primary endpoint of 6-month progression-free survival rate (Abstract 4005).

Breast Cancer

Stephanie Walker on Increasing the Participation of Black Women With Metastatic Breast Cancer in Clinical Trials

Stephanie Walker, a former nurse and current activist with the Metastatic Breast Cancer Alliance, discusses findings from the BECOME project (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement). They show that, even though Black patients comprise between 4% and 6% of all clinical trial participants, Black women with metastatic breast cancer are willing to consider taking part if steps were taken to increase their awareness, build trust through clear communication with health-care providers, involve people of shared racial/ethnic identity and health experience, and help patients find and access trials (Abstract 1014).

Lung Cancer

Rami Manochakian, MD, on NSCLC: Clinical Implications of Findings on Nivolumab Plus Chemotherapy

Rami Manochakian, MD, of Mayo Clinic Florida, discusses the phase II findings of the NADIM II trial, which confirmed that, in terms of pathologic complete response as well as the feasibility of surgery, combining nivolumab and chemotherapy was superior to chemotherapy alone as a neoadjuvant treatment for locally advanced, resectable stage IIIA non–small cell lung cancer (Abstract 8501).

Gynecologic Cancers

Ursula A. Matulonis, MD, and Nicoletta Colombo, MD, on Ovarian Cancer: Overall Survival Data on Relacorilant Plus Nab-Paclitaxel

Ursula A. Matulonis, MD, of Dana-Farber Cancer Institute, and Nicoletta Colombo, MD, of the University of Milan and the European Institute of Oncology, discuss phase II results on the overall survival benefit of intermittent relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel, compared with nab-paclitaxel alone in patients with recurrent platinum-resistant ovarian cancer. A phase III trial comparing intermittent relacorilant plus nab-paclitaxel with investigator’s choice of chemotherapy in primary platinum-refractory disease is ongoing (Abstract LBA5503).