Eligibility for Bevacizumab as an Independent Prognostic Factor for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study

Abstract

BackgroundBevacizumab requires some unique eligibility criteria, such as absence of hemoptysis and major blood vessel invasion by the tumor. The prognostic impact of these bevacizumab-specific criteria has not been evaluated.MethodsPatients with stage IIIB/IV, non-squamous non-small cell lung cancer who started chemotherapy before the approval of bevacizumab were reviewed. Patients with impaired organ function, poor performance status or untreated/symptomatic brain metastasis were excluded before the evaluation of bevacizumab eligibility. We compared overall survival and time to treatment failure among patients who were eligible (Group A) or ineligible (Group B) to receive bevacizumab.ResultsAmong 283 patients with stage IIIB/IV non-squamous non-small cell lung cancer, eligibility for bevacizumab was evaluated in 154 patients. Fifty-seven patients were considered ineligible (Group B) based on one or more of a history of hemoptysis (n = 20), major blood vessel invasion (n = 43) and cardiovascular disease (n = 8). The remaining 97 patients were classified into Group A. Overall survival was significantly better in Group A (median, 14.6 months) than in Group B (median, 7.1 months; p<0.0001). Time to treatment failure was also significantly longer in Group A (median, 6.9 months) than in Group B (median, 3.0 months; p<0.0001). Adjusted hazard ratios of bevacizumab eligibility for overall survival and time to treatment failure were 0.48 and 0.38 (95% confidence intervals, 0.33–0.70 and 0.25–0.58), respectively.ConclusionEligibility for bevacizumab itself represents a powerful prognostic factor for patients with non-squamous non-small cell lung cancer. The proportion of patients who underwent first-line chemotherapy without disease progression or unacceptable toxicity can also be biased by bevacizumab eligibility. Selection bias can be large in clinical trials of bevacizumab, so findings from such trials should be interpreted with extreme caution.

Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy

“…This result supports the concept that eligibility for BEV represents a favorable prognostic factor, in accordance with the findings of a retrospective study by Takagi et al (9). In addition, patients who were eligible for maintenance therapy were found to have a better prognosis, which was expected, as patients with induction therapy failure were excluded.…”

Comparative Effectiveness of Adjunctive Bevacizumab for Advanced Lung Cancer: The Cancer Research Network Experience

“…However, given that the overall outcome in CP-treated patients is our study was much worse than in the ECOG 4599 trial (8.8 vs 10.3 months), coupled with the fact that eligibility for bevacizumab itself represents a powerful prognostic factor for patients with NS-NSCLC, 33 limitations of this study include not being able to determine from the available data whether some of the improvements in overall survival seen in the BCP group should be attributed instead to differences in known (or unknown) but unmeasured treatment and prognostic factors. Specifically, limitations of this study include the absence of measures including weight loss, ECOG performance status, biomarkers, baseline pulmonary function, or the location or number of sites of disease, dose of each chemotherapeutic regimen, median number of cycles of each regiment, use of bevacizumab as maintenance therapy, second line or salvage therapy after CP or BCP, achievement of parity in toxicity-related deaths between the regimens, or disproportionate use of other services, such as additional lines of therapy (i.e., pemetrexed, EGFR-receptor inhibitors, etc.)…”

Renal insufficiency is the leading cause of double maintenance (bevacizumab and pemetrexed) discontinuation for toxicity to advanced non-small cell lung cancer in real world setting

“…Favorable median survival reflects the fact that our population was selected, and it is known that eligibility for bevacizumab is a good prognostic factor [30]. Furthermore, those patients did not progress after the end of the induction chemotherapy.…”