ICON7: Ovarian cancer, platinum second-line chemotherapy and overall survival

Abstract

Background: The ICON7 trial reported increased progression-free survival with beva-cizumab (bev) added to platinum-based chemotherapy in newly-diagnosed ovarian cancer, and increased overall survival (OS) in a poor prognosis subset. Most patients (pts) had further chemotherapy following progression. On average, pts receiving bev had later progression and were thus more likely to receive further platinum. We investigated the effect of second-line treatment type on the association between first-line bev and OS. Methods: Second line chemotherapy regimens were categorised as platinum-containing or other. Platinum reuse varied with time to progression after end of 1 st line (excl. maintenance bev) and also varied between centres. We categorised centres as high or low platinum use, from the proportion of their pts progressing in 0-8 months (mths) and retreated with platinum. The association between 1 st line bev and OS was analysed separately at low-use centres and at high-use centres. Standard survival analysis techniques and methods appropriate for data with non-proportional hazards were used. Results: ICON7 randomised 1528 pts 1:1 to reference treatment þ/-bev. Reference pts were more likely to experience disease progression 8 mths (38% v 24%). Reuse of platinum varied with time to progression; 37% at 0-5 mths; 76% at 6-8 mths; 94% at 9 mths. 174 centres (covering 1290 pts) had 1 progression at 0-8 mths, 76 centres were classed low-use (<50% platinum 2 nd line in 0-8mths) and 98 high-use. The earlier progression of reference pts resulted in fewer getting 2 nd line platinum at low use centres (41% v 56%), but not at high-use centres (76% v 77%). There was evidence of significantly shorter OS among reference pts at low-use centres (p ¼ 0.05, restricted mean survival 44.1 v 49.0 mths), but not at high-use centres (p ¼ 0.20, restricted mean survival 52.2 v 50.0 mths). Conclusions: Improved OS with bevacizumab may result from an association with platinum-containing second line treatment: bev increases time to progression, increased time to progression increases the likelihood of second line platinum, second line platinum increases OS. It is possible therefore that OS might be improved by a lower time threshold for second line platinum chemotherapy, whether or not bevacizu-mab has been used. Background: The standard of care for patients (pts) with recurrent ovarian cancer (OC) who respond to platinum-based chemotherapy has been "watchful waiting". While studies have shown that pts experience anxiety and fear of recurrence during watchful waiting, the rate of serious clinical events that require hospitalizations or emergency room (ER) visits during this observation period has not been examined. The objective of this study was to assess the rate of such events using a claims database. Methods: This retrospective study identified pts newly diagnosed with OC in January 2009 to September 2015 in MarketScan V R Commercial and Medicare Supplemental Databases (US). Pts with commercial or Medicare coverage for 12 months prior to and 1 month after first diagnosis were included. Recurrence was defined by the presence of 2nd-line platinum-based therapy, and watchful waiting as the period without active treatment following chemotherapy. Rate of inpatient admissions and ER visits during watchful waiting were assessed. Results: 1312 pts were identified who had a treatment-free interval after 2nd-line platinum treatment. During this watchful waiting period (median duration, 162 days), 30.1% had an inpatient admission and 27.4% had an ER visit. Median time to first hospitalization from end of 2nd-line chemotherapy was 56 days, and median time to first ER visit was 68 days. There was a total of 650 inpatient hospitalizations, for an average