Predicting response to chemotherapy
The prognostic nomogram called Sarculator was used effectively to define a high-risk subgroup of patients likely to benefit from adjuvant chemotherapy, Sandro Pasquali, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy and his colleagues reported at the meeting.
Perioperative chemotherapy was shown to afford no survival advantage over observation in the EORTC 62931 (European Organization for Research and Treatment of Cancer—62931) study of adjuvant doxorubicin plus ifosfamide (Lancet Oncol 2012;13:1045-54). However, subsequent analyses of that data attributed this finding to variations in treatment schedules and the inclusion of low-risk tumors, which may have diluted the effect of chemotherapy, the researchers said in their abstract.
Further, a recent interim report of the ISG-1001 trial showed a survival benefit for patients who received neoadjuvant epirubicin plus ifosfamide therapy for localized high-risk soft-tissue sarcoma of the extremities or trunk wall (Lancet Oncol 2017;18:812-822).
The researchers performed a retrospective analysis of individual data for 290 patients with extremity and trunk wall soft-tissue sarcomas in the EORTC-STBSG 62931 study. The Sarculator was used to calculate 10-year predicted probability of overall survival (pr-OS) for each patient.
Patients were grouped in two categories of predicted overall survival: high predicted survival (over 60%) and low predicted overall survival (60% or less). Overall survival and disease-free survival were calculated at 8 years, the study’s median follow-up.
The 8-year probability of overall survival and disease-free survival was 58% [95% confidence interval (CI): 52–63%] and 51% (95% CI: 46–57%), respectively. In the 290 patients with extremity and trunk wall soft tissue sarcomas, adjuvant chemotherapy was not associated with an overall survival benefit [Hazard ratio (HR) = 0.91, 95%CI 0.63–1.31]. The Sarcolator Nomogram detected 80 patients who were at greater risk of death compared to the 210 patients with higher predicted overall survival. The risk of death was significantly lower with adjuvant chemotherapy in the group with low predicted survival based on the Sarculator Nomogram (HR=0.50, 95%CI 0.30-0.90). Consistently, the risk of recurrence was significantly lower when adjuvant chemotherapy was used in the group with predicted overall survival of less than 60% (HR = 0.49, 95%CI 0.28-0.85) while this difference was not observed in patients with high predicted overall survival (HR = 0.95, 95%CI 0.62-1.44).
Doxorubicin plus dacarbazine deserve evaluation in prospective trials in leiomyosarcoma
Doxorubicin plus dacarbazine appeared to best the outcomes seen with doxorubicin plus ifosfamide and with doxorubicin alone in terms of overall response rate and progression free survival as first-line treatment in patients with advanced leiomyosarcomas, based on a retrospective analysis presented by Lorenzo D’Ambrosio, MD, of the Unitversity of Torino, Italy, and his associates.
As patients in the trial were not randomized to therapy, the researchers used a logistic regression model that accounted for histology, site of primary, age, gender, performance status, tumor extent, and tumor grade. Patients were then matched across the different groups by their propensity scores.The 303 patients, 216 of them women, were enrolled from 18 EORTC STBSG (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group) sites. Doxorubicin plus dacarbazine was given to 117 patients (39%), doxorubicin plus ifosfamide was given to 71 (23%), and doxorubicin alone was given to 115 (38%). There were no significant differences among the regimens in terms of dose reductions of more than 10%, delays of greater than 72 hours, or granulocyte-colony stimulating factor use.
In the whole population, unadjusted median progression free survival was 9.4 months (95% CI 6.1-9.7 months) for those given doxorubicin plus dacarbazine, 6.8 months (4.5-9.5 months) for those given doxorubicin plus ifosfamide), and 5.4 months (3.8-6.8 months) for those given doxorubicin alone. The respective overall response rates for the three regimens were 36.8%, 21.5%, and 25.9%. When using propensity scores to adjust for lack of randomization, progression free survival was significantly longer with doxorubicin plus dacarbazine [median 9.2 months (95%CI 5.2-9.7 months) than with doxorubicin [median 4.8 months (2.3-6.0 months); HR 0.72 (0.52-0.99)]. The difference was not significant when compared to doxorubicin plus ifosfamide [8.2 months (5.2-10.1 months), HR 1.01 (0.68-1.50)]. Progression free survival did not differ significantly between doxorubicin plus ifosfamide, and doxorubicin [HR 0.71 (0.48-1.06)]. In the same matched population, overall response rates were 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin, respectively.
Overall survival comparisons were weakened by a shorter median follow-up in the doxorubicin plus dacarbazine groups (32 months) compared to the doxorubicin plus ifosfamide group (50 months) and the doxorubicin group (46 months). With this limit, patients in the doxorubicin plus dacarbazine arm had longer overall survival [median 36.8 (27.9-47.2) months] when compared to both doxorubicin plus ifosfamide [21.9 (16.7-33.4), HR 0.65 (0.40-1.06); and doxorubicin arms 30.3 (21.0-36.3) months, HR 0.66 (0.43-0.99).
Subsequent treatments were well balanced across arms. None of the selected factors for multivariate analysis (age, sex, ECOG performance status, histotype, site of primary tumor, tumor grade, and tumor extent) significantly affected the progression free survival and overall survival associated with the treatments.