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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

5537 - Role of TP53 mutations in relation to response to anti-ALK agents in EML4-ALK-translocated NSCLC patients

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Matteo Canale

Citation

Annals of Oncology (2018) 29 (suppl_8): viii649-viii669. 10.1093/annonc/mdy303

Authors

M. Canale1, A. Delmonte2, C. Dazzi3, A. Gamboni4, C. Casanova3, M. Papi5, M. Mariotti2, N. De Luigi2, M.A. Burgio2, G. Minuti6, D. Calistri1, M. Bonafè1, L. Crinò2, P. Ulivi1

Author affiliations

  • 1 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 - Meldola/IT
  • 2 Medical Oncology, Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori (IRST)- IRCCS, 47014 - Meldola/IT
  • 3 Medical Oncology, Umberto I Hospital, 48022 - Lugo/IT
  • 4 Medical Oncology, Degli Infermi Hospital, 48018 - Faenza/IT
  • 5 Medical Oncology, Ospedale Infermi, 47900 - Rimini/IT
  • 6 Medical Oncology, Santa Maria delle Croci, 48121 - Ravenna/IT
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Resources

Abstract 5537

Background

EML4-ALK translocation is a predictive mutation for responsiveness to anti-ALK drugs, and it is present in 3-7% cases of NSCLC patients. Though patients are usually responsive to targeted therapy against EML4-ALK translocation, about 30-40% show drug resistance. We analyzed the impact of TP53 mutations on response to anti-ALK treatment in EML4-ALK-translocated NSCLC patients.

Methods

83 EML4-ALK-translocated NSCLC patients were enrolled, and TP53 status was evaluated in 61 patients, on the basis of DNA availability. Of these patients, 28 patients received an anti-ALK agent in second-or-more line treatment and follow up data were available. TP53 status was considered in relation to disease control rate (DCR: complete response [CR], partial response [PR] or stable disease [SD]).

Results

In the overall case series, TP53 mutations were observed in 14 (23%) patients, 6 (43%), 1 (7%), 3 (21%) and 4 (28%) in exon 5, 6, 7 and 8, respectively. We found 1 insertion (7%), 1 deletion (7%) and 12 point mutations (86%). In the subgroup of 25 patients treated with an anti-ALK agent and evaluable clinical response, TP53 mutations were observed in 5 (20%) patients, 2 (40%), 1 (20%) and 2 (40%) in exon 5, 6 and 8, respectively. The DCR was 60% in TP53-mutated patients with respect to 92% in TP53 wild type (wt) patients. Three patients had a non evaluable clinical response, as they early stopped anti-ALK agent treatment due to rapid PD/deterioration of general conditions and they succumbed to their disease in a few weeks. Two of these where found with a stop mutation in exon 5.

Conclusions

TP53 mutations are associated with a worse DCR in EML4-ALK-translocated NSCLC patients treated with an anti-ALK agent. These results highlight the importance of tumor-suppressor genes in determining response to TKIs. Data analysis for PFS and OS of patients are ongoing.

Clinical trial identification

Legal entity responsible for the study

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) – IRCCS.

Funding

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) – IRCCS.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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