Trends in Anemia Treatment Among Patients with Non-Myeloid Malignancies Treated with Chemotherapy

Background: Anemia is a common complication of chemotherapy that can cause clinically important symptoms and reduced quality of life. It is unclear how management of chemotherapy induced anemia (CIA) has evolved over time given the changes in the US prescribing information, reimbursement, and implementation of a risk evaluation and mitigation strategy (REMS) for the use of erythropoiesis-stimulating agents (ESAs).

Objective: To describe treatment trends and current treatment patterns for anemia during chemotherapy in 2000 to 2013.

Methods: Patients diagnosed with incident breast, lung, colorectal, ovarian or gastric cancer who developed moderate to severe anemia (i.e., grade II-IV based on the CTCAE grading system, or hemoglobin <10 g/dl) during chemotherapy were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of anemia episodes with the following CIA treatment modalities: use of ESA, red blood cell (RBC) transfusion, iron, folate or B12 nutritional therapy or no treatment by anemia severity in three calendar periods: January 2000-Dec 2006 (P1), January 2007-24 March 2010 (P2), 25 March 2010-June 2013 (P3). We also estimated the most recent hemoglobin concentrations in the 7 days before ESA and RBC transfusion. Differences between calendar periods were assessed for proportions treated and for hemoglobin concentration prior to CIA treatment. Standard errors were estimated with use of the generalized estimating equations.

Results: A total of 7,266 patients were included in this study (3,374 breast, 1,751 lung, 1,406 colorectal, 503 ovarian and 232 gastric cancer). Overall, 16% of the patients were diagnosed at stage I, 31% at stage II, 30% at stage III and 23% at stage IV. The mean age at diagnosis was 60 years. The observed grade II-IV anemia episodes were 1741 (7,159 pts) in P1, 880 (3,285 pts) in P2, and 1011 (3699 pts) in P3. Figures 1 and 2 show the proportion of various CIA treatment modalities by CIA severity. Proportion of anemia episodes with ESA use decreased from 2006 to 2013 (P1: 28%; P2: 21%; and P3: 3%). An increased trend of transfusion use was observed (P1: 8%; P2: 14%; and P3: 16%), with the greatest increase observed in grade III CIA (P1: 21%; P2: 41%; and P3: 54%). There was also an increase in the proportion of untreated CIA (P1: 66%; P2: 68%; and P3: 80%). When we examined the level of hemoglobin concentration prior to CIA intervention, there was a slight decrease in the hemoglobin concentrations prior to ESA use across calendar periods [mean (SD): 9.7 (1.1) g/dl in P1; 9.6 (1.1) in P2; 9.1 (1.2) in P3, p<0.01], but no difference was found for hemoglobin concentrations prior to RBC transfusion [mean (SD): 8.3 (1.3) in P1; 8.4 (1.5) in P2; 8.4 (1.3) in P3]. Iron, folate or B12 nutritional therapy was more common in severe CIA (i.e. grade III-IV, Figure 2), with a small decreasing trend in use across calendar periods (P1: 10%; P2: 8%; and P3: 7%).

Similar trends for CIA treatment modalities across the three calendar periods were observed when we restricted the analyses to stage 4 cancer (Figure 3).

Conclusion: The study indicates that along with the decreased utilization of ESA, utilization of RBC transfusion has increased significantly over the calendar periods in patients diagnosed with five solid tumors. Approximately 80% of patients with moderate to severe anemia (Hg < 10g/dL) in patients of these common solid tumors remained untreated in most recent calendar period (March 25, 2010–June 30, 2013).