Repotrectinib Shows Promising Activity in ROS1+ NSCLC

Excerpt:

“Repotrectinib (TPX-0005) demonstrated a clinically meaningful and durable benefit across multiple doses in patients with ROS1 fusion–positive non–small cell lung cancer (NSCLC).

“Overall response rates (ORRs) were 80% for tyrosine kinase inhibitor (TKI)-naïve patients (95% CI, 44-97) and 18% for TKI-refractory patients (95% CI, 4-44), including 33% for those who received a dose of 160 mg once daily, according to findings from the ongoing phase I/II TRIDENT-1 study. Interim analysis results were presented at the 19th World Conference on Lung Cancer (WCLC).”

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LOXO-292 Safe, Effective for RET-Altered Non-Small Cell Lung Cancer

Excerpt:

“LOXO-292 appeared well tolerated and demonstrated antitumor activity among patients with heavily pretreated RET fusion-positive non-small cell lung cancer, according to updated interim results of a global, phase 1/phase 2 trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.

“Researchers reported initial clinical data from the LIBRETTO-001 dose escalation/expansion study of LOXO-292 (Loxo Oncology) — an oral and selective agent in clinical development for cancers that harbor abnormalities in the rearranged during transfection (RET) kinase — at ASCO Annual Meeting in June.”

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Novel Agent Active in ROS1-Mutant NSCLC

Excerpt:

“Three-fourths of patients with ROS1-positive non-small cell lung cancer (NSCLC) had objective responses lasting an average of 2 years with an investigational multikinase inhibitor, a preliminary trial showed.

“Overall, 41 of 53 patients responded to treatment with entrectinib, including 17 of 33 patients with central nervous system (CNS) metastases at baseline. Responses had a median duration of 24.6 months among patients without CNS metastases and 13.6 months among those with CNS metastases.”

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Poziotinib Shows Encouraging Activity Among Heavily Pretreated NSCLC Subgroup

Excerpt:

“Poziotinib (NOV120101, HM781-36B) demonstrated high antitumor activity in patients with metastatic, heavily pretreated EGFR and HER2 exon 20 mutant non–small cell lung cancer (NSCLC), according to phase II study results presented at the 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada.

To date, the agent specifically induced a best response rate of 55%, including a 43% confirmed objective response rate (ORR) among evaluable patients with EGFR exon 20 mutant NSCLC in the study, said John V. Heymach, MD, PhD, who presented data of the investigator-initiated study of poziotinib in EGFR and HER 2-exon 20 mutant NSCLC (NCT03066206).”

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First-Line Atezolizumab Plus Chemotherapy Improves PFS for Lung Cancer

Excerpt:

“The addition of frontline atezolizumab to carboplatin or cisplatin plus pemetrexed improved PFS among patients with non-small cell lung cancer, according to interim results from a global phase 3 randomized trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.

“IMpower132 is an open-label study of atezolizumab (Tecentriq, Genentech) — a PD-L1 inhibitor — among 578 chemotherapy-naive patients with stage IV nonsquamous NSCLC. Exclusion criteria included EGFR or ALK mutations, untreated central nervous system metastases, autoimmune disease and prior exposure to immunotherapy.”

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Pembrolizumab Alone or With Chemotherapy for PD-L1–Positive NSCLC?

Excerpt:

“Researchers found that in patients with non–small-cell lung cancer (NSCLC) and a Tumor Proportion Score (TPS) ≥ 50, pembrolizumab plus chemotherapy failed to improve overall survival (OS) or progression-free survival (PFS) compared with pembrolizumab alone.

“Results from the study were presented in a poster presentation at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer, held September 23–26 in Toronto.”

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Brigatinib Superior to Standard of Care Crizotinib in ALK+ NSCLC

Excerpt:

“Adult patients with ALK-positive, locally advanced or metastatic non–small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor experienced a more than 50% reduction in the risk of disease progression or death with treatment with brigatinib (Alunbrig), compared with the first-line standard of care, crizotinib.

“Brigatinib demonstrated superior progression-free survival (PFS) compared with crizotinib, corresponding to a 51% reduction in the risk of disease progression or death (HR, 0.49; 95% CI, 0.33-74; P = .0007), according to first interim analysis results presented at the 19th World Conference on Lung Cancer and simultaneously published in the New England Journal of Medicine.”

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Hyperprogression in NSCLC Patients With PD-1/PD-L1 Inhibitors

Excerpt:

“Hyperprogressive disease (HPD) occurred more commonly among patients with pretreated non-small cell lung cancer (NSCLC) receiving PD-1 (programmed cell death protein 1)/PD-L1 (ligand 1) inhibitors than in patients treated with chemotherapy, according to the results of a study published in JAMA Oncology.

“Among those patients with hyperprogressive disease – defined as disease progression at first evaluation with a variation per month exceeding 50% – treated with immunotherapy there was a higher metastatic burden and poorer prognosis, compared with patients without hyperprogressive disease.”

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Studies Confirm Osimertinib Activity in Brain Mets

Excerpt:

“The resistance mutation-targeting EGFR inhibitor osimertinib (Tagrisso) demonstrated superior activity against central nervous system (CNS) metastases as compared with chemotherapy or nonselective EGFR inhibitors, two randomized trials of patients with lung cancer showed.

“In a comparison involving patients with untreated EGFR-mutated advanced non-small cell lung cancer (NSCLC), the median CNS progression-free survival (PFS) was not reached in patients who received osimertinib or a first-generation EGFR inhibitor. However, the available data favored the osimertinib arm (95% CI 16.5 months to not reached versus 13.9 months to not reached, HR 0.48, 95% CI 0.26-0.86, P=0.014). Osimertinib also led to a higher response rate.”

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