Large Cell Neuroendocrine Carcinomas (Lcnec) of the Lung: Pathologic Features, Treatment and Outcomes

Naidoo, Jarushka; Santos-Zabala, Maria L.; Iyriboz, Tunc; Woo, Kaitlin M.; Sima, Camelia S.; Fiore, John J.; Kris, Mark G.; Veach, Stephen R.; Riely, Gregory J.; Iqbal, Afsheen; Smith-Marrone, Stephanie; Sarkaria, Inderpal S.; Krug, Lee M.; Rudin, Charles M.; Rekhtman, Natasha; Pietanza, M. Catherine

doi:10.1093/annonc/mdu345.11

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“…Eligible pathologic diagnoses include adenocarcinoma, large-cell carcinoma, sarcomatoid carcinoma, adenosquamous carcinoma, and nsclc not otherwise specified. Patients not eligible for ALK testing are those with "pure" squamous-cell, small-cell, and large-cell neuroendocrine carcinoma [49][50][51][52][53] . However, ALK testing can be considered for atypical patients, such as a lifetime never-smoking individual with squamous-cell carcinoma.…”

Section: Alk Testingmentioning

confidence: 99%

Canadian Perspectives: Update on Inhibition of ALK-Positive Tumours in Advanced Non-Small-Cell Lung Cancer

Melosky¹,

Cheema

Agulnik

et al. 2018

Current Oncology

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BackgroundInhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update.MethodsClinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive nsclc.ResultsRandomized phase iii trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase ii trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation alk tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows:Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALKrearrangement.Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.Patients progressing on alk tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.Other systemic therapies should be exhausted before immunotherapy is considered.SummaryMultiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALKrearrangement.

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