2024 October 3rd release

This release contains 993 approved relationships.

Added entries:

• (FDA) EGFR p.L858R and exon 19 deletions and sensitivty to amivantamab-vmjw in combination with carboplatin and pemetrexed for the treatment of patients with non-small cell lung cancer.
• (FDA) EGFR p.L858R and exon 19 deletions and sensitivty to osimertinib for the treatment of patients with non-small cell lung cancer.

Revised entries:

• (FDA) RET somatic variants and sensitivity to selpercatinib for the treatment of patients with medullary thyroid cancer received an approval from the FDA, previously accelerated approval.
• (FDA) The description of three records corresponding to FDA approved indications for osimertinib were edited for clarity.
• (FDA) Six records for capivasertib in combination with fulvestrant incorrectly categorized fulvestrant as a targeted therapy. It has been updated to be a hormone therapy, and the therapy_type for each of these records has been updated to be "Combination therapy".
• (Clinical evidence) The PMID for Bostner et al. was incorrected listed as "7486065" instead of "17486065". The evidence category was also changed from Clinical evidence to Clinical trial. Thank you, Cameron Grisdale!

Four records listed therapy type either as "Targeted therapy + Chemotherapy", "Targeted therapy + Chemotherapy + Chemotherapy", or "Chemotherapy + Targeted therapy + Chemotherapy" instead of "Combination therapy". These records have been updated.

2024 September 5 release

This release contains 989 approved relationships.

Added entries:

• (FDA) IDH1 and IDH2 somatic variants and sensitivity to vorasidenib for patients with astrocytoma and oligodendroglioma. Specifically, IDH1 p.R132C, p.R132G, p.R132H, p.R132L, p.R132S, and IDH2 p.R172K and p.172G.
• (FDA) EGFR p.L858R and exon 19 deletions and sensitivity to lazertinib in combination with amivantamab for patients with non-small cell lung cancer.

2024 July 11 release

Added entries:

• (FDA) KRAS p.G12C and sensitivity to adagrasib in combination with cetuximab for patients with colorectal cancer received accelerated approval.
• (FDA) NTRK1/2/3 gene fusions and sensitivity to repotrectinib for patients with solid tumors received accelerated approval.

Revised entries:

• (FDA) RET fusions and sensitivity to selpercatinib for patients with thyroid cancer received traditional approval from the FDA, from accelerated approval.

2024 June 6 release

Added entries:

• (FDA) ALK fusions and sensitivity to alectinib for patients with non-small cell lung cancer.
• (FDA) BRAF p.V600E/K (p.V600 variants), rearrangements, and fusions and sensitivity to tovorafenib for patients with low-grade glioma.
• (FDA) EGFR p.L858R and exon 19 deletions and sensitivity to erlotinib for patients with non-small cell lung cancer.
• (FDA) EGFR p.L858R and exon 19 deletions and sensitivity to gefitinib for patients with non-small cell lung cancer.

Revised entries:

• (FDA) RET fusions and sensitivity to selpercatinib for patients with solid tumors is now indicated for pediatric patients aged 2 and older, in addition to adult patients.
• (FDA) RET fusions and sensitivity to selpercatinib for patients with thyroid cancer is now indicated for pediatric patients aged 2 and older, revised from age 12 or older.
• (FDA) RET variants and sensitivity to selpercatinib for patients with medullary thyroid cancer is now indicated for pediatric patients aged 2 and older, revised from age 12 or older.
• (FDA) RET fusion and sensitivity to selpercatinib for patients with non-small cell lung cancer's description and publication date were revised.

2024 April 11 release

Added entries:

• (FDA) ABL1 p.T315I and sensitivity to ponatinib for patients with acute lymphoid leukemia.
• (FDA) ABL1 p.T315I and sensitivity to ponatinib for patients with chronic myeloid leukemia.
• (FDA) BCR::ABL1 and sensitivity to ponatinib in combination with chemotherapy for patients with acute lymphoid leukemia.
• (FDA) BCR::ABL1 and sensitivity to ponatinib for patients with acute lymphoid leukemia.

Revised entries:

• The therapeutic strategy for two records with ROS inhibition were changed to ROS1 inhibition
• MRE11A somatic variants and sensitivity to enzalutamide in combination with talazoparib for patients with prostate cancer was updated to have the gene symbol be MRE11

All records were also updated to have a _deprecated field, which is a boolean value to hide the record from appearing on https://moalmanac.org.

2024 March 7 release

Added entries:

• (FDA) ALK fusions and sensitivity to crizotinib for patients with anaplastic large cell lymphoma.
• (FDA) EGFR exon 20 insertions and sensitivity to amivantamab-vmjw in combination with carboplatin and pemetrexed for patients with non-small cell lung cancer.
• (FDA) EGFR exon 19 deletions or p.L858R and sensitivity to osimertinib in combination with cisplatin and pemetrexed for patients with locally advanced or metastatic non-small cell lung cancer.
• (FDA) EGFR exon 19 deletions or p.L858R and sensitivity to osimertinib for patients with metastatic non-small cell lung cancer.
• (FDA) MET exon 14 splice site and deletion variants (exon 14 skipping) and sensitivity to tepotinib for patients with metastatic non-small cell lung cancer.

Revised entries:

• (FDA) ALK rearrangement and sensitivity to crizotinib, updated publication date from 2016-06-01 to 2011-08-26.
• (FDA) ALK fusion and sensitivity to crizotinib in patients with Inflammatory Myofibroblastic Tumors (IMT), removed EML4 as a required fusion partner and updated publication date from 2022-07-01 to 2022-07-14.
• (FDA) EGFR p.T790M and sensitivity to osimertinib, updated citation and publication date to reflect March 2017 approval (from accelerated approval) date for this indication.
• (FDA) EGFR exon 20 insertions and sensitivity to amivantamab-vmjw, updated publication date from 2021-05-01 to 2021-05-21.
• (FDA) EGFR exon 19 deletions or p.L858R and sensitivity to osimertinib as an adjuvant therapy for patients with metastatic non-small cell lung cancer, updated publication date from 2020-12-01 to 2020-12-11.
• (FDA) MET exon 14 splice site and deletion variants (exon 14 skipping) and sensitivity to capmatinib for patients with metastatic non-small cell lung cancer was updated to reflect the change from accelerated approval to approval in August 2022.
• (FDA) ROS1 fusions and sensitivity to crizotinib, updated publication date from 2016-06-01 to 2016-03-11.
• (Clinical trial) ATM nonsense, splice site, and frameshift variants and sensitivity to BAY 1895344 was revised to update its citation from an abstract (doi:10.1200/JCO.2019.37.15_suppl.3007) to the study's journal publication (pmid:32988960).
• (Clinical trial) MET amplification and sensitivity to crizotinib in patients with non-small cell lung cancer was revised to update its citation from an abstract (doi:10.1200/JCO.2018.36.15_suppl.9062) to the study's journal publication (pmid:33676017).

Removed entries:

• (FDA) MET exon 14 nonsense variants and sensitivity to capmatinib in patients with non-small cell lung cancer.
• (Guideline) MET exon 14 nonsense variants and sensitivity to crizotinib in patients with non-small cell lung cancer.

The U.S. FDA also granted accelerated approval to lifileucel for patients with unresectable or metastatic melanoma, but a drug label is not yet present for lifileucel. Our standard operating procedure was updated to no longer allow Abstracts as an evidence source for the knowledge base.

2024 February 1 release

Added entries:

• (FDA) BRAF p.V600E/K and sensitivity to vemurafenib for patients with Erdheim-Chester disease.

Revised entries:

• (FDA) BRCA1/2 somatic variants and sensitivity to rucaparib for patients with fallopean tube cancer had the oncotree term updated to High-Grade Serous Fallopian Tube Cancer.
• (FDA) FGFR3 fusions, p.R248C, p.S249C, p.G370C, and p.Y373C and sensitivity to erdafitinib for patients with urothelial carcinoma received an updated approval.
• "Oncogenic Mutations" was removed from the variant_annotation field from all 10 records with that value.

Removed entries:

• (FDA) FGFR2 fusions and sensitivity to erdafitinib for patients with urothelial carcinoma. The FDA amended their prior accelerated approval for erdafitinib, removing susceptible FGFR2 alterations from the indication.

2024 January 11 release

Added entries:

• (FDA) ERBB2 amplification and sensitivity to neratinib in combination with capecitabine for patients with breast cancer.

Revised entries:

• (FDA) ERBB2 amplification and sensitivity to neratinib for patients with breast cancer, received an updated description and citation.

The description or context within 14 records also received minor updates to improve clarity.

In addition, we updated our S.O.P. for curating clinical guidelines from the NCCN to reflect their referencing guide. All relevant records within this database were updated in our November 2023 release.

2023 December 7 release

Added entries:

• (FDA) PIK3CA and AKT somatic variants and PTEN loss of function variants and sensitivity to capivasertib in combination with fulvestrant for patients with breast cancer.
• (FDA) ROS1 rearrangements and sensitivity to repotrectinib in patients with nsclc.

Revised entries:

• (FDA) ERBB2 amplification and sensitivity to pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum- containing chemotherapy for patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma received an updated indication from the FDA.
• (FDA) NTRK1/2/3 rearrangements and sensitivity to larotrectinib were changed from translocation to fusion rearrangement type.
• EGFR p.L858R entries now all contain information for exon and rsid values
• ABL1 p.T315I entries were revised to have consistent exon and rsid values
• NRAS p.G12C entries now include an rsid
• The OncoTree terms and codes were swapped for ATK1 missense variants and p.E17K and sensitivity to MK-2206 in breast cancer and ATM knockdowns in colorectal cancer

Removed entries:

• (Clinical evidence) PTEN deletions and resistance to pembrolizumab in uterine leimyoma (Peng et al. 2016) had a duplicate entry in the knowledge base, which has been removed.

2023 November 9 release

Database content: v.2023-11-09
Database schema: 1.2.0

This month's data release features recent FDA approvals, updates of mutational signatures from version 2 to 3.4, updates to the source fields for several citations, removal of several entries, revising format of all clinical guideline citations, and the publication_date field has been populated for all current database records.

Added entries:

• (FDA) BCR::ABL1 and sensitivity to bosutinib for pediatric patients with CML.
• (FDA) BRAF p.V600E and sensitivity to encorafenib in combination with binimetinib for adult patients with NSCLC.
• (FDA) IDH1 p.R132C, p.R132H, and somatic variants and sensitivity to ivosidenib for patients with myelodysplastic syndromes (MDS).
• (Guideline) FLT3 p.D835A, p.D835E, p.D835H, p.D835Y and poor prognosis in patients with MDS.
• (Guideline) GATA2 missense, nonsense, frameshift, and splice site variants and poor prognosis in patients with MDS.
• (Guideline) NPM1 p.W288Cfs*12 and poor prognosis in patients with MDS.
• (Guideline) NRAS p.G12A, p.G12C, p.G12D, p.G12R, p.G12S, p.G12V, p.G13A, p.G13D, p.G13R, p.G13V, p.Q61E, p.Q61H, p.Q61L, p.Q61P, and p.Q61R and poor prognosis for patients with MDS.
• (Guideline) SETBP1 p.I865N and poor prognosis for patients with MDS.
• (Guideline) SF3B1 p.I704S and poor prognosis for patients with MDS.
• (Guideline) SRSF2 p.P95A, p.P95H, p.P95L, p.P95R, and p.P95_R102del and poor prognosis for patients with MDS.
• (Guideline) TP53 missense, nonsense, splice site, and frameshift variants and poor prognosis for patients with MDS.
• (Guideline) U2AF1 p.S34A, p.S34F, p.S34Y, p.Q157P, p.Q157R and poor prognosis for patients with MDS.

Revised entries:

• (FDA) NTRK1/2/3 fusions and sensitivity to entrectinib were revised due to the FDA's approval for adult or pediatric patients older than 1 month with any solid tumor.
• (Guideline) PDGFRB translocations and sensitivity to imatinib in mds was revised to match updated guidelines that specify ETV6 as a fusion partner and CMML as a more specific tumor type.
• (Guideline) TET2 variants and sensitivity to Azacitidine was downgraded from Guideline to Clinical evidence.
• (Preclinical) BRAF p.V600E and sensitivity to dabrafenib in combination with either omipalisib (PI3K/Akt/mTOR) or bevacizumab (VEGF/VEGFR) was revised to add clinical context and expand upon the relationship description.
• All Mutational Signature relationships (17) have been updated from version 2 to version 3.4.
• The citation text was updated for Bostner et al. 2007 (PMID: 7486065), Leone et al. 2008 (PMID: 18829482), Corcoran et al. 2010 (PMID: 21098728), Sillars-Hardebol et al. 2012 (PMID: 22207630), Dickson et al. 2013 (PMID: 23569312), Etemadmoghadam et al. 2013 (PMID: 24218601), Johung et al. 2013 (PMID: 23897899), Van Allen et al. 2014 (PMID: 25096233), Wagle et al. 2014 (PMID: 24265154), Gorre et al. 2016 (PMID: 11423618), Luo et al. 2016 (PMID: 27580028), Cuppens et al. 2017 (PMID: 28232476), and Willliams et al. 2020 (PMID: 28283584).
• The DOI and/or URL were updated for Takano et al. 2005 (PMID: 15998907), Fong et al. 2009 (PMID: 19553641), Tesser-Gamba et al. 2012 (PMID: 22154052), Chatterjee et al. 2013 (PMID: 23565244), Hunter et al. 2014 (PMID: 24937673), Mak et al. 2015 (PMID: 25450872), Fondello et al. 2016 (PMID: 27399807), Hugo et al. 2016 (PMID: 26997480), Ke et al. 2016 (PMID: 27717507), Sung et al. 2016 (PMID: 27793752), George et al. 2017 (PMID: 28228279), Mouw et al. 2017 (PMID: 28630051), Aldubayan et al. 2018 (PMID: 29478780), Seligson et al. 2018 (PMID: 30541756), De Bono et al. 2019, and Tewari et al. 2021 (PMID: 34496240). Many of these changes are due to a recently discovered issue with DOIs pointing to journals published through Elsevier.
• The NCT code was updated for Le et al. 2015 (PMID: 26028255)

Removed entries,

• (Guideline) BCR::ABL1 and sensitivity to dasatinib, imatinib, and nilotinib in CML to reduce redundency from other CML guideline entries.
• (Guideline) BRAF p.V600E and sensitivity to dabrafenib in combination with trametinib in patients with NSCLC. This citation was incorrectly categorized as a Guideline as it references an FDA approval, which has since been added to the knowledge base.
• (Guideline) BRCA1/2 germline variants and sensitivity to pazopanib in ovarian cancer because the underlying source does not mention this relationship in the context of BRCA1/2.
• (Guideline) BRCA2 germline variants and sensitivity to olaparib in ovarian cancer, as there was a duplicate record.
• (Guideline) KIT variants and poor prognosis in head and neck mucosal melanoma, as the citation suggests that head and neck mucosal melanoma has a poor prognosis independent of KIT status.
• (Guideline) KRAS, _PRFPF8_variants and poor prognosis in MDS. While KRAS is included in the IPSS-M Prognostic Risk Schema, KRAS being highlight as associated with poor prognosis is not explicitly stated in current guidelines.
• (Guideline) NRAS, SETBP1, TP53 variants and poor prognosis in MDS has been removed as the current guidelines cite specific amino acid changes, which have been added.
• (Clinical trial) EGFR variants and sensitivity to Durvalumab + Gefitinib in NSCLC was removed per further studies observing a negative finding.
• (Clinical trial) KRAS p.G12C and sensitivity to AMG 510 was removed because there are now associated FDA approvals, and we will be phasing out abstracts from the knowledge base.
• (Clinical evidence) NRAS p.Q61L and sensitivity to Selumetinib in MDS was removed as it contained a duplicate record.
• (Preclinical) BRAF p.V600E and sensitivity to GANT61 was removed because the study findings were independent of melanoma cell line BRAF or NRAS status.