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This is another nail in the anti-TIGIT coffin. In more than 500 patients with untreated PD-L1–high non–small cell lung cancer (NSCLC), adding tiragolumab to atezolizumab missed both primary endpoints, and the numerical progression-free survival (PFS) and overall survival (OS) gains never reached significance. What it did add was toxicity: twice the grade 3–4 adverse events (AEs) and more discontinuations. Together with the other failed TIGIT programs, this pretty much closes the door on chemo-free anti-TIGIT combinations in first-line NSCLC, so single-agent PD-(L)1 or chemo-IO stays the standard for these patients.

Progression-free survival (PFS) was higher in the Sun group vs chemotherapy, 10.3 m vs 7.5 m with HR of .65 with higher responses (58.9% vs 31.1%) diarrhea high CK and anemia were the most common side effects. The issue is that amivan was not part of treatment and compared to chemotherapy ami in addition to chemotherapy had 11m PFS also in this trial few had brain mets so no evaluation for CNS protection or treatment. But an oral agent in patients who don’t want to come to the office often.

109 patients with stage II or IIIA disease, 2-year investigator-assessed event-free survival was 92% with selpercatinib and 61% with placebo (HR for disease recurrence, progression, or death, 0.17 P<0.001). Patients with stage IB, II, or IIIA non–small-cell lung cancer (NSCLC), event-free survival at 2 years was 94% with selpercatinib and 70% with placebo. Genomic testing is expanding now for early stage NSCLC. More study in the adjuvant setting showing promise with targeted therapy.

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.

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.