Survival analysis of patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitor (TKI) treatment: A multi-center retrospective study

Aims and background Bone flare reaction as a sign of response to antineoplastic treatment has been redefined, including the onset of new osteoblastic lesions. If misunderstood as skeletal progression, this finding could lead to erroneous therapy discontinuation, changing the disease clinical course. We aim to describe this clinical phenomenon in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) gene-activating mutations treated with tyrosine kinase inhibitor (TKI). Methods We retrospectively reviewed the computed tomography scans of 43 EGFR-mutated patients with NSCLC treated with EGFR-TKI, analyzing the bone response in terms of increase in the quantity and/or density of lesions, and assessing objective tumor response to treatment. Results Osteoblastic reaction was detected in 10 cases (23%), showing different patterns: dimensional or density increase of known osteosclerotic metastases (pattern A, n = 4); response of previously lytic lesions (pattern B, n = 2); onset of new osteosclerotic lesions (pattern C, n = 4). Seven patients had partial response to TKI treatment, with response rate of 70%, vs 50% of patients with bone metastases without this reaction. No difference in terms of median overall survival or progression-free survival emerged between patients with or without osteoblastic reaction. Conclusions The correct clinico-radiologic interpretation of osteoblastic reaction is crucial to avoid waste of therapeutic lines when TKI treatment has not yet exhausted its potential effectiveness. Clinical implications of ambiguous radiologic findings as described in this study deserve further discussion.

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Evaluation of immune-related adverse events in patients treated with sequential immunotherapy and tyrosine kinase inhibitor treatment in non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21562 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21562-e21562

Author(s):

Angel Ray Baroz ◽

Isa Mambetsariev ◽

Jeremy Fricke ◽

Rebecca Pharaon ◽

Dan Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Tyrosine Kinase ◽

Small Cell Lung Cancer ◽

Tyrosine Kinase Inhibitor ◽

Kinase Inhibitor ◽

Small Cell ◽

Small Cell Lung ◽

Tki Treatment ◽

Nsclc Patients

e21562 Background: Immune-related adverse events (irAEs) have been frequently observed with non-small cell lung cancer (NSCLC) patients treated with immunotherapy (IO). The severity of irAEs in response to IO treatment may reflect antitumor response. The effect of irAEs with sequential IO and tyrosine kinase inhibitor therapies has not been fully characterized. This study aims to evaluate the irAEs in NSCLC patients who have received sequential IO and TKI treatment. Methods: A retrospective cohort of 387 NSCLC patients previously treated with IO was identified from the City of Hope Thoracic Registry (THOR) from February 2010 to January 2020. Patients had confirmed pathologic disease and received IO and TKI, either on clinical trial or as standard of care. IO-treated patients were classified into two groups: TKI vs non-TKI treated. The non-TKI IO-treated group was used to verify that outcomes are not dependent on the immunotherapy given, but rather TKI therapy. IrAEs were collected from treatment courses and assessed based on the treating physician diagnosis. Results: A total of 63 NSCLC patients received sequential IO and TKI treatment. Histology was nonsquamous in 59 (93.7%) and squamous in 4 (6.3%). Multiple lines of therapies were accounted for in each patient. IO therapies received included nivolumab (n = 30), pembrolizumab (n = 24) and atezolizumab (n = 11). Mostly frequently used TKI therapies were erlotinib (n = 43), osimertinib (n = 25), afatinib (n = 11), crizotinib (n = 10), gefitinib (n = 5), and alectinib (n = 4). IrAEs occurred in 23 patients (36.5%). 22/23 (95.7%) patients who reported irAEs received TKI treatment prior to receiving IO treatment. The most common irAEs were pneumonitis (n = 5), diarrhea (n = 4), fatigue (n = 3) and rash/pruritus (n = 3). Other irAEs included arthralgias & myalgias (n = 2), new onset diabetes (n = 1) and renal insufficiency (n = 1). Conclusions: The severity of irAEs and sequential IO and TKI treatment in NSCLC patients is still not well-defined. Overall and progression-free survival were considered in this cohort. Preliminary data suggested that EGFR-TKI treated patients have low response to immune checkpoint inhibitors, but outcomes vary by allele variation. Further prospective analyses are needed to investigate the correlation of irAEs and survival outcomes with TKI-resistant NSCLC patients treated with IO. Also, treating physician’s diagnosis of irAEs exposed a need to clarify grade and severity of irAEs.

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