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First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations

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.

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Selpercatinib in Early-Stage RET Fusion–Positive Non–Small-Cell Lung Cancer

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.

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Ensartinib in Resected ALK-Positive Non–Small-Cell Lung Cancer

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.

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First-Line Zongertinib in Advanced HER2-Mutant Non–Small-Cell Lung Cancer

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.

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Setidegrasib in Advanced Non–Small-Cell Lung Cancer and Pancreatic Cancer

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.

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Setidegrasib in Advanced Non–Small-Cell Lung Cancer and Pancreatic Cancer

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.

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Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2

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.

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