Patients Whose Treatment Included Bevacizumab Were More Likely to Experience Toxicity but Less Likely to Be Hospitalized

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A study among patients with advanced non–small cell lung cancer (NSCLC) treated with carboplatin-paclitaxel or carboplatin-paclitaxel-bevacizumab (Avastin) found that those receiving the triplet were more likely to experience a toxicity event but less likely to be hospitalized within 180 days after the start of chemotherapy. “Findings here confirm the need for adherence to clinical recommendations for judicious use of carboplatin-paclitaxel-bevacizumab but provide reassurance regarding the relative risk for hospitalization,” researchers reported in the Journal of Oncology Practice.

The study involved 1,109 patients with stages IIIB-IV NSCLC aged ≥ 21 years diagnosed between 2005 and 2010 and treated with first-line carboplatin-paclitaxel or carboplatin-paclitaxel-bevacizumab at four health maintenance organizations. Follow-up continued through December 31, 2011. The researchers, affiliated with those four health maintenance organizations and Fred Hutchinson Cancer Research Center in Seattle, used data about patient and tumor characteristics and hospital and ambulatory encounters in the 180 days after chemotherapy initiation to evaluate the association between carboplatin-paclitaxel and carboplatin-paclitaxel-bevacizumab and toxicities and hospitalizations.

“Describing the patterns of toxicity profiles and hospitalizations associated with bevacizumab use in a community setting is important because it directly addresses the need for more clinically relevant information regarding the potential balance of benefits and harms for an expensive drug that may confer only limited improvements in survival,” the authors noted.

Most patients received carboplatin-paclitaxel, 911 (82%) vs 198 (18%) who received carboplatin-paclitaxel-bevacizumab. “Patients who received carboplatin-paclitaxel-bevacizumab were younger and were more likely to have had stage IV disease and well- or moderately differentiated tumors,” the researchers observed.

Toxicity and Hospitalization

Approximately 57% of the carboplatin-paclitaxel-bevacizumab patients and 53% of the carboplatin-paclitaxel patients had evidence of any toxicity event (P = .40). Patients treated with carboplatin-paclitaxel-bevacizumab “had significantly more bleeding, proteinuria, and GI perforation events (all P < .05),” the investigators found. The finding of significantly more toxicity events among patients receiving carboplatin-paclitaxel-bevacizumab was “consistent with earlier randomized clinical trials,” the authors noted.

Overall, 34% of patients receiving carboplatin-paclitaxel vs 19% of patients receiving carboplatin-paclitaxel-bevacizumab had at least one hospitalization (P < .001). “Both unadjusted and adjusted models showed that patients who received carboplatin-paclitaxel-bevacizumab were less likely than patients who received carboplatin-paclitaxel to experience a hospital-related event after the initiation of chemotherapy,” the researchers wrote.

The unadjusted odds ratio associated with the likelihood of patients who received carboplatin-paclitaxel-bevacizumab having a hospitalization was 0.46 (95% confidence interval [CI], 0.32–0.67). Using multivariable and propensity score–adjusted models, the odds ratio for patients who received carboplatin-paclitaxel-bevacizumab being hospitalized was 0.48 (95% CI, 0.32–0.71). Patients receiving carboplatin-paclitaxel-bevacizumab also had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47–0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47–0.60) than patients who received carboplatin-paclitaxel.

With these findings, “we rejected the null hypothesis that in the presence of a higher toxicity burden, the likelihood of a hospitalization after the initiation of bevacizumab would increase after the adjustment for observable factors, including age and comorbidity status,” the authors stated. “To our knowledge, this is the first study outside of a clinical trial setting to examine these outcomes in patients with NSCLC.”

Clinical Implications

The findings of this study “have international implications, building on analyses of toxicities and costs recently reported for targeted cancer therapies,” according to an accompanying editorial by Terhi T. Hermanson, MD, PhD, of Helsinki University Hospital, Finland, and three colleagues from the United States. “Whereas toxicities associated with carboplatin-paclitaxel-bevacizumab may be relatively constant from country to country, therapy-related hospitalizations will differ because of variations both between and within health systems. Although this study is directed toward oncologists and decision makers in the United States, other audiences will benefit from it.”

The editorial continued: “The authors have made a terrific beginning in analyzing the impact of a new cancer regimen for NSCLC in a community setting in the United States. Updates are essential as experience with this regimen matures internationally and as new NSCLC regimens are introduced. For the time being, caveat emptor to clinicians who choose to administer carboplatin-paclitaxel-bevacizumab therapy to patients with NSCLC; toxicities are significant with this regimen, even among younger patients with few comorbid illnesses.”  ■

Carroll NM, et al: J Oncol Pract 11:356-362, 2015.

Hermanson TT, et al: J Oncol Pract 11:363-364, 2015.