Benefit observed with adjuvant chemoradiotherapy
In a multicenter, international, randomized phase 3 trial, known as the PORTEC-3 trial, de Boer and colleagues sought to determine if combined adjuvant chemoradiation improved overall survival (OS) and failure-free survival when compared with external-beam radiation therapy (EBRT) alone in the treatment of women with high-risk endometrial cancer.7 Women were eligible for the study if they had histologically confirmed stage I, grade 3 endometrioid endometrial cancer with deep invasion and/or lymphovascular space invasion, stage II or III disease, or stage I-III disease with serous or clear cell histology.
Participants were randomly assigned in a 1:1 ratio; 330 women received adjuvant EBRT alone (total dose of 48.6 Gy administered in 27 fractions), and 330 received adjuvant chemotherapy during and after radiation therapy (CTRT) (2 cycles of cisplatin 50 mg/m2 IV given on days 1 and 22 of EBRT followed by 4 cycles of carboplatin AUC 5 and paclitaxel 175 mg/m2 IV every 3 weeks).
At a median follow-up of 73 months, treatment with adjuvant CTRT, compared with adjuvant EBRT alone, was associated with a significant improvement in both overall survival (5-year OS: 81.4% vs 76.1%, P = .034 [FIGURE]) and failure-free survival (5-year failure-free survival: 76.5% vs 69.1%, P = .016).
The greatest absolute benefit of adjuvant CTRT, compared with EBRT alone, in survival was among women with stage III endometrial cancer (5-year OS: 78.5% vs 68.5%, P = .043) or serous cancers (19% absolute improvement in 5-year OS), or both. Significant differences in 5-year OS and failure-free survival in women with stage I-II cancer were not observed with adjuvant CTRT when compared with adjuvant EBRT alone. At 5 years, significantly more adverse events of grade 2 or worse were reported in the adjuvant CTRT arm.
Results from similar trials
Since the publication of results from the updated analysis of PORTEC-3, results from 2 pertinent trials have been published.8,9 In the GOG 249 trial, women with stage I-II endometrial cancer with high-risk features were randomly assigned to receive 3 cycles of carboplatin-paclitaxel chemotherapy with vaginal brachytherapy or EBRT.8 There was no difference in survival, but a significant increase in both pelvic and para-aortic recurrences were seen after the combination of chemotherapy and vaginal brachytherapy.8
In GOG 258, women with stage III-IVA endometrial cancer were randomly assigned to receive chemotherapy alone (carboplatin-paclitaxel) or adjuvant chemotherapy after EBRT.9 No differences in recurrence-free or overall survival were noted, but there was a significant increase in the number of vaginal and pelvic or para-aortic recurrences in patients in the chemotherapy-only arm.9
WHAT THIS EVIDENCE MEANS FOR PRACTICE
The conflicting data regarding the ideal adjuvant therapy for endometrial cancer suggests that treatment decisions should be individualized. Pelvic EBRT with concurrent adjuvant chemotherapy should be considered in women with stage III endometrial cancer or serous cancers as combination therapy improves survival, although dual modality treatment is associated with increased toxicity. Chemoradiation appears to have less benefit for women with stage I–II cancers with other pathologic risk factors.
The conflicting data regarding the ideal adjuvant therapy for endometrial cancer suggests that treatment decisions should be individualized. Pelvic EBRT with concurrent adjuvant chemotherapy should be considered in women with stage III endometrial cancer or serous cancers as combination therapy improves survival, although dual modality treatment is associated with increased toxicity. Chemoradiation appears to have less benefit for women with stage I–II cancers with other pathologic risk factors.
Role for PARP inhibitor plus first-line chemotherapy, and as maintenance therapy, in ovarian cancer treatment
Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403-2415.
Ovarian cancer is the leading cause of gynecologic cancer-related deaths among women in the United States.10 Treatment consists of cytoreductive surgery combined with platinum and taxane-based chemotherapy.11 Despite favorable initial responses, more than 80% of patients experience a recurrence, with an 18-month median time to progression.12 As a result, recent efforts have focused on finding novel therapeutic approaches to improve treatment outcomes and mitigate the risk of disease recurrence.
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