It seems the old cliche of more drugs than patients is becoming true for most providers here. The data needs to mature further here but likely this will be another option for Anaplastic lymphoma kinase (ALK)+ non–small-cell lung cancer (NSCLC) patients in the adjuvant setting. It does look like CNS protection benefits are meaningful as well.
The median overall survival (OS) was 27·9 months with ivonescimab versus 23·7 months with tis.
Median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 m) this is regardless of PDL-1 expression (1-49 or >50).
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.
This update demonstrated that encorafenib plus binimetinib was associated with the longest median overall survival (mOS) reported to date among targeted therapies in patients with treatment-naïve BRAF V600E–mutant metastatic NSCLC (mNSCLC). Median OS was 47.6 months in treatment-naïve patients. By the way check the authors there 😊.
PACIFIC-2 was a phase III trial testing durva given concurrently with cCRT (and continued as consolidation) versus placebo + cCRT in unresectable stage III NSCLC, and it did not meet its primary endpoint. The overall response rate (ORR) was essentially identical (60.7% vs 60.6%), and pneumonitis rates were similar (any grade 28.8% vs 28.7%; grade ≥3: 4.6% vs 5.6%), but adverse events (AEs) leading to discontinuation and fatal AEs were higher with durva (25.6% vs 12.0%; 13.7% vs 10.2%), especially early on. Starting IO up front with cCRT didn’t improve outcomes and added early toxicity—consolidation durva after cCRT is still the way to go.