Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non–small cell lung cancer (NSCLC) and no progression after definitive, concurrent chemoradiotherapy (cCRT). Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further.
Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT. Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression. The primary end point was progression-free survival (PFS) by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), the proportion of patients alive 24 months (OS24), and safety.
In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109). There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio [HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively. Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, −15.2 to 16.3%]; P = .976). With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%.
Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.
Confirmed objective response was 76% the median duration of response was 15.2 months and the median progression-free survival (PFS) was 14.4 months Of the patients with brain mets 47% had a confirmed intracranial objective response Zongertinib showed sustained efficacy in previously untreated patients with advanced or metastatic HER2-mutant Non–Small-Cell Lung Cancer (NSCLC) with mostly low-grade toxicity.
45 patients with Non–Small-Cell Lung Cancer (NSCLC) who received the 600-mg dose, 36% had a partial response, the median progression-free survival (PFS) was 8.3 months, estimated 12-month overall survival was 59% 21 patients with metastatic pancreatic ductal adenocarcinoma 24% had a response, the median PFS was 3.0 months and the median overall survival was 10.3 months.
Setidegrasib represents a meaningful advance in targeting KRAS G12D–mutant tumors, demonstrating a 36% response rate with median PFS exceeding 8 months in heavily pretreated NSCLC, and a 24% response rate with ~10 month median overall survival (OS) in third line pancreatic cancer, both notable signals in populations lacking approved targeted therapies.
The CHRYSALIS-2, the cohort C analysis of patients with atypical EGFR mutations showed meaningful and durable activity. Atypical mutations can be difficult to deal with as a clinician, and having concrete data on these (S768I, L861Q and G719ZX) mutations gives assurance that this doublet is active. Overall response rate (ORR) was 52% and median progression-free survival (PFS) was 11.1 months in refractory patients and 19.5 months in the treatment-naive population.
The final overall survival (OS) analysis from the FLAURA2 confirms the well-published findings that Osi + chemo improves survival over Osi monotherapy. OS difference was about 10 months at 47 vs 37 months, with a predictable toxicity tradeoff.