How Do Payers Respond to Regulatory Actions? The Case of Bevacizumab

PURPOSE: In February 2008, the US Food and Drug Administration (FDA) granted accelerated approval for bevacizumab for metastatic breast cancer. After public hearings in July 2010, and June 2011, the FDA revoked this approved indication in November 2011, on the basis of additional evidence regarding its risk/benefit profile. The Centers for Medicare and Medicaid Services, local Medicare contractors, and commercial payers varied in their stated intentions to cover bevacizumab after FDA's regulatory actions. We examined payer-specific trends in bevacizumab use after the FDA's regulatory actions. METHODS: We used outpatient medical claims compiled by IMS Health to evaluate trends in bevacizumab use for breast cancer for Medicare-insured and commercially insured patients (N = 102,906) using segmented regression. Given that Medicare coverage policies may vary across regional contractors, we estimated trends in bevacizumab use across 10 local coverage areas. In a sensitivity analysis, we estimated trends in bevacizumab use for breast cancer compared with trends in use for lung cancer using difference-in-differences models. RESULTS: Among chemotherapy infusions for breast cancer, bevacizumab use decreased from 31% in July 2010, to 4% in September 2012. Use decreased by 11% among commercially insured and 13% among Medicare-insured patients after July 2010 (interaction P = .68) and continued to decline by 9% per month (interaction P = .61). We observed no contractor-level variation in bevacizumab use among Medicare beneficiaries. During the same period, bevacizumab use for lung cancer was stable. CONCLUSION: Although insurers varied in public statements regarding coverage intentions, bevacizumab use declined similarly among all payers, suggesting that provider decision making, rather than payer-specific coverage policies, drove reductions

The role of PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: a network meta-analysis

Background: Tumor programmed death ligand one (PD-L1) expression has been studied in several trials in non-small-cell lung cancer. Methods: We assessed the potential role of PD-L1 expression according to Cochrane Collaboration's Guidelines. Results: 13 studies with 1979 patients were included. Among 915 PD-L1 negative patients this rate was 13% (RR 2.08; 95% CI: 1.49-2.91; p < 0.01). The response rate has increased concurrent to the PD-L1 expression (Pearson's correlation, r = 0.43). PD-L1 expression was also related to better 24-weeks progression-free rate (RR 0.79; 95% CI: 0.71-0.89) and a trend toward better 1-year overall survival rate (RR 0.96; 95% CI: 0.87-1.06). Conclusion: Taking this data in account, PD-L1 overexpression could not be currently considered a robust biomarker to tailor the immune checkpoint inhibitors treatment

Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study.

BACKGROUND: Amivantamab plus carboplatin-pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. PATIENTS AND METHODS: A total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab-lazertinib-chemotherapy, chemotherapy, or amivantamab-chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab-lazertinib-chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. RESULTS: All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR-, and MET-related toxicities. Amivantamab-chemotherapy had lower rates of hematologic AEs than amivantamab-lazertinib-chemotherapy. CONCLUSIONS: Amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab-lazertinib-chemotherapy regimen