METHODS AND MATERIALS FOR PREDICTING RESPONSE TO NIRAPARIB
This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of homologous recombination deficiency (HRD) or an HRD signature to predict response to niraparib. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an HRD signature to predict response to niraparib are provided.
1 . An in vitro method of predicting patient response to a cancer treatment regimen comprising niraparib, the method comprising:
(1) determining in a patient sample the number of Indicator CA Regions comprising at least two types chosen from Indicator LOH Regions, Indicator TAI Regions, or Indicator LST Regions in at least two pairs of human chromosomes of a breast cancer cell; and
(2) diagnosing a patient in whose sample said number of Indicator LOH Regions, Indicator TAI Regions, and/or Indicator LST Regions is greater than a reference number as having an increased likelihood of responding to said cancer treatment regimen.
2 . The method of claim 1 , wherein said at least two pair of human chromosomes is representative of the entire genome.
3 . The method of claim 1 , wherein said Indicator CA Regions are determined in at least ten pairs of human chromosomes.
4 . The method of claim 1 wherein the Indicator CA Regions analyzed in said patient sample comprise Indicator LOH Regions, Indicator TAI Regions, and Indicator LST Regions.
5 . The method of claim 4 wherein a Combined CA Region Score is calculated from the number of Indicator CA Regions and in step (2) a patient in whose sample said Combined CA Region Score is greater than a reference Combined CA Region Score is diagnosed as having an increased likelihood of responding to said cancer treatment regimen.
6 . The method of claim 1 wherein the reference number is 5 or greater.
7 . The method of claim 6 wherein the reference number is 42.
8 . The method of claim 5 wherein the reference Combined CA Region Scores is 5 or greater.
9 . The method of claim 8 , wherein the reference Combined CA Region Score is 42.
10 . The method of claim 1 , further comprising administering said cancer treatment regimen to said patient diagnosed as having an increased likelihood of responding to said cancer treatment regimen.
11 . The method of claim 1 , wherein the step of determining comprises hybridizing nucleic acids from the sample with probes.
12 . An in vitro method of predicting patient response to a cancer treatment regimen comprising niraparib, the method comprising:
(1) determining in a patient sample the number of Indicator CA Regions comprising at least two types chosen from Indicator LOH Regions, Indicator TAI Regions, or Indicator LST Regions in at least two pairs of human chromosomes of a breast cancer cell;
(2) providing a test value derived from the number of said Indicator CA Regions;
(3) comparing said test value to one or more reference values derived from the number of said Indicator CA Regions in a reference population; and
(4) diagnosing a patient in whose sample said test value is greater than said one or more reference numbers as having an increased likelihood of responding to said cancer treatment regimen.
13 . The method of claim 12 , wherein said at least two pair of human chromosomes is representative of the entire genome.
14 . The method of claim 12 , wherein said Indicator CA Regions are determined in at least ten pairs of human chromosomes.
15 . The method of claim 14 , wherein the Indicator CA Regions analyzed in said patient sample comprise Indicator LOH Regions, Indicator TAI Regions, and Indicator LST Regions.
16 . The method of claim 15 , wherein a Combined CA Region Score is calculated from the number of Indicator CA Regions and in step (2) a patient in whose sample said Combined CA Region Score is greater than a reference Combined CA Region Score is diagnosed as having an increased likelihood of responding to said cancer treatment regimen.
17 . The method of claim 12 wherein the reference number is 5 or greater.
18 . The method of claim 17 wherein the reference number is 42.
19 . The method of claim 16 wherein the reference Combined CA Region Scores is 5, 6, 7, 8, 9, 10, 11, 12, 12, 1/1, 15, 16, 18, 19, 20, 22, 2/1, 26, 28, 20, 22, 34-36-33-40-42-44-46-48-50 or greater.
20 . The method of claim 19 , wherein the reference Combined CA Region Score is 42.
21 . The method of claim 12 , further comprising diagnosing a patient in whose sample said test value is not greater than said one or more reference numbers as not having an increased likelihood of responding to said cancer treatment regimen and either (5)(a) recommending, prescribing, initiating or continuing a treatment regimen comprising niraparib in said patient diagnosed as having an increased likelihood of responding to said cancer treatment regimen; or (5)(b) recommending, prescribing, initiating or continuing a treatment regimen not comprising niraparib in said patient diagnosed as not having an increased likelihood of responding to said cancer treatment regimen.
22 . The method of claim 12 , comprising diagnosing a patient in whose sample said test value is at least 25% greater than said one or more reference numbers as having an increased likelihood of responding to said cancer treatment regimen.
23 . The method of claim 12 , wherein the determining comprises hybridizing nucleic acids from the sample with probes.
24 . A method of treating cancer patients, comprising:
(1) determining in a patient sample the number of Indicator CA Regions comprising Indicator LOH Regions, Indicator TAI Regions, and Indicator LST Regions in at least two pairs of human chromosomes of a breast cancer cell;
(2) providing a test value derived from the number of said Indicator CA Regions;
(3) comparing said test value to one or more reference values derived from the number of said Indicator CA Regions in a reference population; and either
(4)(a) recommending, prescribing, initiating or continuing a treatment regimen comprising niraparib in a patient in whose sample the test value is greater than at least one said reference value; or
(4)(b) recommending, prescribing, initiating or continuing a treatment regimen comprising niraparib in a patient in whose sample the test value is not greater than at least one said reference value.
25 - 34 . (canceled)
35 . A method of analyzing a tumor sample, the method comprising the steps of:
(1) providing a tumor sample from a subject suffering from cancer, whose potential response to a cancer treatment regimen comprising niraparib is to be determined, wherein the tumor sample comprises nucleic acid;
(2) determining a value for Indicator CA Regions in the nucleic acid, which value incorporates numbers of at least two types of Indicator Regions selected from the group consisting of Indicator LOH Regions, Indicator TAI Regions, Indicator LST Regions, and combinations thereof, for at least two pairs of human chromosomes from cells in the tumor sample; and
(3) comparing the determined value with that of a corresponding reference value from a comparable tumor sample or samples from tumor(s) with known responsiveness to niraparib.
36 - 45 (canceled)