Lung Cancer—Non-Small Cell Metastatic

Shun Lu, Xiaorong Dong, Hong Jian, et al.
The authors of the study conclude that aumolertinib - a novel, irreversible epidermal growth factor receptor tyrosine kinase inhibitor - significantly prolonged progression-free survival and duration of response compared to gefitinib as first-line therapy in advanced NSCLC with EGFRm. They observed a favorable safety profile with aumolertinib, especially regarding toxicities mediated by wild-type EGFR. For the study authors, aumolertinib is a promising option for advanced NSCLC with EGFRm. Clinical trial information: NCT03849768
Suresh S. Ramalingam, Caicun Zhou, Tae Min Kim, et al.
The authors of the study conclude that mobocertinib - a first-in-class, potent, oral TKI targeting EGFR ex20ins mutations - showed clinically meaningful benefit for patients with EGFR ex20ins+ mNSCLC in platinum-pretreated patients anddose-escalation/expansion and extension cohorts. Mobocertinib showed a manageable safety profile. Clinical trial information: NCT02716116
Julien Mazieres, Claire Lafitte, Charles Ricordel, et al.
The authors of the study conclude that the triple combination with trastuzumab, pertuzumab and docetaxel is feasible and active in HER2 pretreated advanced NSCLC. The study confirms the activity of HER2 antibodies-based strategy which, according to the authors should be considered in these patients. Clinical trial information: NCT03845270
Luis G. Paz-Ares, Tudor-Eliade Ciuleanu, Jong-Seok Lee, et al.
The authors of the study conclude that first-line nivolumab plus ipilimumab continued to provide durable, long-term overall survival benefit versus chemotherapy in advanced NSCLC regardless of PD-L1 expression or histology. Clinical trial information: NCT02477826
William A. Stokes, Madhusmita Behera, Renjian Jiang, et al.
The authors of the study conclude from this largest analysis to date of antibiotic therapy in NSCLC patients receiving immune checkpoint inhibitor, that receipt of antibiotic therapy within either 30 days before or 60 days after start of immune checkpoint inhibitor was associated with lower overall survival. This suggests, that antibiotic therapy may have a detrimental effect on immunotherapy outcomes.
Biagio Ricciuti, Kathryn Cecilia Arbour, Joao Victor Machado Alessi, et al.
The authors of the study conclude that a very high tumor mutational load is associated with better outcomes to immune checkpoint inhibitor and a distinct immunophenotype in NSCLC. Rational integration of tumor mutational load and PD-L1 expression may identify NSCLCs most likely to respond to immune checkpoint inhibitor treatment.
Lisa Derosa, Bertrand Routy, Laurence Zitvogel, et al.
The authors of the study conclude that the validation of the prognostic role of Akkermansia muciniphila in patients with NSCLC (stratification based on the bacterias relative abundance represents a more accurate independent predictor than the binary modality) provides the rationale to develop a microbiome-based approach to study gut dysbiosis in routine clinical oncology care. Clinical trial information: NCT04567446
Juergen Wolf, Edward B. Garon, Harry J.M. Groen, et al.
The authors of the study conclude that results of Cohort 7 confirm those previously reported for Cohort 5b showing higher efficacy of capmatinib when used as 1st-line in METex14 NSCLC patients. A clinically meaningful median overall survival of 20.8 months in 1st-line (Cohort 5b) and of 13.6 months in relapse (Cohort 4) was also observed.  Together with the continued manageable toxicity profile, the data support capmatinib as a valuable targeted treatment option for METex14 NSCLC patients. Clinical trial information: NCT02414139
Xiuning Le, Luis G. Paz-Ares, Jan Van Meerbeeck, et al.
METamp is an oncogenic driver in 1–5% of patients with NSCLCs. It confers a poor prognosis and lacks approved targeted therapies. The authors of the study conclude that In the first study of a MET inhibitor in NSCLC with METamp prospectively detected by liquid biopsy, tepotinib - a highly selective MET inhibitor - showed high and clinically meaningful activity, especially in 1st-line treatment. According to the study authors, Tepotinib was generally well tolerated and warrants further evaluation in NSCLC with METamp. Clinical trial information: NCT02864992
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Jyoti D. Patel, Xiuning Le, Remi Veillon, Ian Churchill Anderson, et al.
The authors of the study conclude that tepotinib showed a robust systemic activity in patients with METex14 skipping NSCLC with brain metastases.
This is complemented by intracranial activity in an ad hoc analysis using Neuro-Oncology Brain Metastases (RANO-BM) criteria. There should be considered the mall patient numbers, a large proportion of patients with prior radiotherapy for brain metastases, and the retrospective nature of the analysis. Prospective evaluation of intracranial activity data from VISION Cohort C is ongoing. Clinical trial information: NCT02864992
Hiroshige Yoshioka, Toyoaki Hida, Hiroshi Nokihara,et al.
The authors of the study conclude that prolongation of overall survival in the alectinib arm was not observed compared to the crizotinib arm. The overall survival result may be substantially confounded since 78.8% of the patients in the crizotinib arm received alectinib as initial, subsequent therapy. Clinical trial information: 132316.
Rafal Dziadziuszko, Xiao Li, Eric C. Anderson, et al.
The authors of the study show that up to 21% of patients may not receive 1st-line treatment. Patients with TP53 co-mut appear to have favorable outcomes, while those with STK11 and/or KEAP1 co-mut appear to have inferior outcomes versus patients without these mut. The lack of PD-L1 testing in many patients indicates a lack of tissue for comprehensive tissue testing. This highlights a potential benefit of blood-based detection of biomarkers, including KRASG12C. Clinical trial information: NCT03178552
Jonathan W. Riess, Mary Weber Redman, Paul Wheatley-Price, et al.
The authors of the study conclude that S1900A failed to show the requisite level of efficacy for rucaparib in advanced NSCLC pts with high genomic loss of heterozygosity and/or a BRCA1/2 mutation. No new safety signals recorded. Hematologic toxicities were the most frequent adverse events.
The authors state that genomic loss of heterozygosity as a phenotypic marker of homologous recombination deficiency does not predict sufficient activity of rucaparib in NSCLC. This is in contrast to the high level of efficacy of PARPi in patients with BRCA-associated or high loss of heterozygosity cancers of other tumor types. Clinical trial information: NCT03845296