“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).”
“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.”
“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.”
“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.”
“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.”
“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.”
“Today, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) in combination with pemetrexed (Alimta) and platinum as first-line treatment of patients with metastatic, nonsquamous non–small cell lung cancer with no EGFR or ALK genomic tumor aberrations.
“Pembrolizumab was previously granted accelerated approval for this indication in May 2017 based on improvements in overall response rate and progression-free survival for patients randomized to pembrolizumab administered with pemetrexed and carboplatin as compared with pemetrexed and carboplatin alone in the KEYNOTE-021 study.”
“In a planned subgroup analysis of the phase III AURA3 trial reported in the Journal of Clinical Oncology, Wu et al found that the third-generation EGFR tyrosine kinase inhibitor osimertinib (Tagrisso) produced higher central nervous system (CNS) response rates vs platinum plus pemetrexed (Alimta) in patients with advanced EGFR T790M-positive non–small cell lung cancer (NSCLC).
“In AURA3, 419 patients with disease progression on prior EGFR tyrosine kinase inhibitor treatment were randomized 2:1 to receive osimertinib at 80 mg once daily or platinum plus pemetrexed. The current subgroup analysis was conducted in patients with measurable or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiologic review.”
“Brigatinib conferred substantial intracranial responses and durable PFS among patients with brain metastases and ALK-positive, non-small cell lung cancer previously treated with crizotinib, according to ongoing study results.
” ‘Crizotinib [Xalkori; Pfizer, EMD Serono], the first licensed ALK inhibitor, is very active but has clear central nervous system liability from poor CNS penetration. All of the next-generation ALK inhibitor drugs have started to show CNS efficacy consistent with their superior activity in the brain compared with crizotinib,’ D. Ross Camidge, MD, PhD, director of thoracic oncology at University of Colorado, told HemOnc Today. ‘The whole clinical trials field has had to evolve around these events in terms of how we should capture and present CNS data. Brigatinib [Alunbrig; Takeda Oncology, Ariad] was one of the drugs that helped with this.’ ”