Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.
In the treatment of non–small-cell lung cancer (NSCLC) with a driver mutation, the role of anti–PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy.
We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS).
A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm.
To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti–PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.
Superior to osi (23 vs 16 progression-free survival). This is more toxic though, but seems manageable. Could this be a new first line standard of care? Also, this includes brain penetration data.
Adding SBRT improves local control and disease progression in the brain but not overall survival. Do the radiation oncologists have input? Is it worth it to control symptoms?
Neoadjuvant Osimertinib did not have a significant impact on major pathologic response and there were no ypCR’s after a median of ~8 weeks of therapy. I do think this shows a measurable response, enough such that I would consider Osi in a patient with “borderline resectable” disease.
Bispecific (a bispecific antibody targeting programmed cell death 1 protein and vascular endothelial growth factor) and chemotherapy … and it worked … second line after EGFR therapy failure.
Osimertinib in adjuvant, now after chemotherapy and radiation, next… Neoadjuvant??? Trials are ongoing.
This is here till progression.
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