Abstract 9007 on Brigatinib update

The initial write up of the abstract 9007 was posted on May 19.

This update covers about 3 more months of data and brain mets.

Arm A (90 mg) median Progression Free Survival (PFS) increased from 8.8 months to 9.2 months. For arm B (180 mg) the median PFS increased from 11.1 months to 12.9 months. Probability of overall survival at 1 year was 71% for arm A and 80% for arm B.

For patients with measurable brain mets at baseline, for arm A the Objective Response Rate was 36% and for arm B the ORR was 67%. Median intracranial PFS was 15.6 months for arm A and not yet reached for arm B.

There is a press release on this topic on Ariad’s website.

Posted in AP26113 - brigatinib from Ariad, Brain metastases, Lung cancer, Potential Treatments, Research | Leave a comment

Outcomes for ALK+ patients

Abstract e20550 is from Spain and involves 49 patients. Patients took 6 different ALK inhibitors. The abstract concluded “ALK+ patients who received targeted agents have prolonged survival despite brain metastases…. ALK inhibitors improve intracranial response rate and survival.”

Posted in 3922 - lorlatinib by Pfizer, alectinib - Alecensa from Chugai - Roche - GenenTech, AP26113 - brigatinib from Ariad, Brain metastases, ceritinib - Zykadia from Novartis, crizotinib - Xalkori from Pfizer, Lung cancer, Potential Treatments, Research | Leave a comment

Discontinuing Crizotinib treatment

Abstract e20610 is from Canada and covers 97 patients. Post Crizotinib treatment 43% received Ceritinib, 20% received chemo and 37% received no additional treatment. Median overall survival was:

0.9 months for those who received no additional treatment,

7.6 months for those who received chemo, and

20.4 months for those received Ceritinib.

Posted in ceritinib - Zykadia from Novartis, crizotinib - Xalkori from Pfizer, Lung cancer, Potential Treatments, Research, Resistance to treatment | Leave a comment

Brain mets

Abstract 9063 combines data from two trials on Alectinib. There were 225 patients. The conclusion reached was that “Alectinib is effective in patients with baseline CNS mets, regardless of prior radiation treatment. Based on the low incidence of CNS progressive disease in patients without CNS mets at baseline, Alectinib may also have a potential preventative effect on patients.”

Abstract e20527 looked at 291 patients in Canada. 141 with and 150 without brain mets. 12% had ALK mutations and 88% had EGFR mutations. They found that the patients without brain mets had a median survival about 2 years longer.

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HSP90 and Crizotinib

Abstract 9059 basically flung that administrating an HSP90 inhibitor at the same time as Crizotinib did not delay the development of resistance to Crizotinib.

Posted in crizotinib - Xalkori from Pfizer, Lung cancer, Potential Treatments, Research, Resistance to treatment, Side Effects | Leave a comment

Alectinib, mutations, and liquid biopsy

Abstract 9061 pooled data from two clinical trials. 129 patients had biopsies done after Crizotinib but before Alectinib. Plasma samples were available for all 272 patients at baseline and for about 50% at progression.

At baseline 13 functional ALK mutations were identified (5 previously unreported). At progression 3 new mutations were seen. At least 7 baseline mutations had median PFS greater than 3 months suggesting Alectinib was active against them. Mutations I1171S/N ans G1202R may occur during treatment.

As for liquid biopsy, “Tumor DNA in plasma may be a non-invasive way to monitor resistance mutations”.

Posted in alectinib - Alecensa from Chugai - Roche - GenenTech, Lung cancer, Potential Treatments, Research, Resistance to treatment | Leave a comment

Crizotinib and children

Abstract 11509 covers 107 pediatric patients and their tumors. ALK alterations were found in 18 of them (not all are fusion mutations). The ages ranged from 3-16 years. 7 patients were still being treated at the data cut off. At least 4 types of cancer were treated. To quote the abstract “Crz was well tolerated” and “children can benefit from crz therapy.” I am not a doctor so I can not compare these patients side effect profile with other similar studies. Among the 8 evaluable patients there was one complete response, 3 partial responses, and 1 stable disease (for a DCR of 5/8 (62.5%)).

Posted in crizotinib - Xalkori from Pfizer, Glioblastomas, Neuroblastomas, Potential Treatments, Research, Side Effects | Leave a comment

Ceritinib and mutations

Abstract 9064 covers 85 patients but only 8 patients has ALK mutations and baseline biopsies collected within 14 days of progression . L1196M was most common. The study indicated that Ceritinib was potent against several known ALK mutations.

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Info on Liquid biopsy

Abstract e20643 is only available online. In this trial, 10,000 solid cancer patients blood were tested by Guardian360 (a method that sequences compete exons (the part of the DNA that encodes for proteins)). Of those patients ALK fusions were detected in 6%. EML4 was the fusion partner in 81% of the patients and 4 other fusion partners made up the rest of the 19%. 24 patients has ALK+ NSCLC. Mutant alleles ranged from 0.06% to 12.5%. They found several Somatic mutations (SNV) of which 10% were known resistance mutations in ALK. They also found other occurring SNV in other genes that are rare or absent in untreated patients suggesting possible novel Crizotinib resistance mechanisms.

Posted in Lung cancer, Research, Uncategorized | Leave a comment

X-396 update and info on liquid biopsy

Abstract 9056 is an update of info previously published on this site.

The study involved 60 patients of whom 30 were ALK+ NSCLC. Of that 30, 19 (60%) had partial responses (PR).

8 patients were Crizotinib naive and of them 7 (88%) had PRs.

12 patients had prior Crizotinib but no other ALK inhibitor, of them 10 (83%) had PRs.

CNS responses have been observed.

As for the liquid biopsy. ALK was detected in the blood plasma of 16 patients, all of whom responded to treatment. Serial sampling and sequencing demonstrated that a decrease in ALK in patients responding and a increase in ALK at the time of progression. These results do not appear to be robust enough to on their own justify routinely doing a liquid biopsy, but rather an area for more in depth research to be done.

Posted in Brain metastases, Lung cancer, Potential Treatments, Research, Side Effects, X-396 - ensartinib from Xcovrery | Leave a comment