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Poster Display session

159P - ReWARD study - Real world ALK resistance data: A single center experience


03 Apr 2022


Poster Display session


Translational Research;  Pathology/Molecular Biology

Tumour Site


Ullas Batra


Annals of Oncology (2022) 33 (suppl_2): S105-S110. 10.1016/annonc/annonc865


U. Batra1, S. Nathany2, M. Sharma2, H. Singh2, A. Mehta1

Author affiliations

  • 1 Rajiv Gandhi Cancer Institute and Research Centre, New Delhi/IN
  • 2 Rajiv Gandhi Cancer Institute and Research Centre, 110085 - New Delhi/IN


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Abstract 159P


ALK rearranged NSCLC has emerged as a distinct entity with growing number of potent ALK tyrosine kinase inhibitors. Despite showing durable responses and promising survival rates, resistance to these ensue. ReWARD is the largest series of repeat biopsies from patients of ALK-positive NSCLC progressing on ALK directed therapy from this part of the world. Using a combinatorial approach of genomics, histology we describe the spectrum of various resistance mechanisms encountered.


This is a cross sectional study recruiting ALK-positive NSCLC cases who have progressed on any line ALK TKI and have undergone repeated biopsies followed by genomic sequencing by NGS.


32 ALK-positive NSCLC patients progressed on TKI were enrolled. Median age was 53 years (range:36-75 years) with a male predilection (male: female- 1.3:1). 27 (84.4%) cases harbored an additional resistance mechanism. Eighteen of these harbored an on-target ALK alteration, with L1196M gatekeeper mutation being the most common, in 11 cases, G1202 alteration in 3 cases. In 9 cases an off-target alteration was detected, the most frequent being TP53 mutation in 8 cases, KRAS mutation in 4 cases and MET amplification in 3 cases. Four patients underwent sequential NGS testing and allele frequency changes in ALK fusion and resistance mechanisms were demonstrated. 16 patients have been offered lorlatinib therapy, the median PFS of which has not yet been reached. Table: 159P

Characteristics Number %
Age: Median 53
Range 36-75 years
Male 18 56.3
Female 14 43.7
Pre-enrolment TKI
Crizotinib 12 37.5
Ceritinib 11 34.4
Alectinib 9 28.1
Post resistance treatment given
Ceritinib 9 28.1
Alectinib 7 21.9
Lorlatinib 16 50


ReWARD is the largest series depicting ALK resistance mechanisms from a single center to date. SPACEWALK study which demonstrated ALK TKI resistance mechanisms using plasma-based genotyping was a multicentric study. The spectrum encountered in ReWARD is distinct from the rest of the world, thus highlighting heterogeneity within ALK-rearranged tumors. Comprehensive clinical evaluation at disease progression coupled with next-generation sequencing-based genotyping will pave the way for lucid understanding of disease biology, thus aiding in the institution of optimal therapy.

Legal entity responsible for the study

Ullas Batra.


Has not received any funding.


All authors have declared no conflicts of interest.

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