Precision Medicine in Oncology®

Multiple FDA approvals and an increasing number of clinical trials examining molecular target–based therapeutics, including second- or even third-generation drugs against a well-defined target, present an ever-widening array of drugs for routine cancer care based on the discovery of specific molecular targets within the tumor or within the germline.

Among the pioneering targets for antibody therapy was CD20, the pursuit of which ultimately led to the first FDA-approved mAb for cancer therapy, rituximab, and defined a new era in the management of B-cell malignancies.

Kaiku Health has announced that they are partnering with the global healthcare company Novartis to develop a digital patient monitoring and management system specifically for patients with melanoma who are receiving BRAF/MEK combination therapies.

In an effort to build on the efficacy demonstrated with ruxolitinib, investigators are evaluating combination therapies—specifically the dual inhibition of the JAK-STAT and BET pathways using pelabresib, a novel BET inhibitor.

Larotrectinib has demonstrated efficacious responses and disease control in patients with TRK fusion–positive central nervous system tumors.

Selumetinib did not elicit clinical activity in pediatric and young adult patients with refractory cancers who had actionable mutations in the RAS/RAF/MAPK1/2-ERK pathway.

The highly selective, central nervous system-active TRK inhibitor larotrectinib yielded promising response rates in patients with TRK fusion cancer, including in those with CNS metastases at baseline.

Pralsetinib demonstrated robust and durable anti-tumor activity, as well as a tolerable safety profile, in heavily pretreated patients with multiple RET fusion–positive advanced solid tumors.

Zenocutuzumab represents a promising novel targeted therapeutic option for patients with NRG1 fusion–positive cancers.

Sotorasib provided continued durable clinical benefit in patients with pretreated KRAS p.G12C–mutated non–small cell lung cancer.

The investigational SHP2 inhibitor TNO155 demonstrated encouraging safety and tolerability, and consistent evidence of SHP2 inhibition in patients with advanced solid tumors.

Melissa (Kah Poh) Loh, BMedSci, MBBCh, BAO, discusses the challenges of utilizing geriatric assessment in oncology and steps that the ACCC resources can provide to institutions that want to incorporate geriatric assessment into practice.

The FDA has approved the Guardant360 CDx assay as a companion diagnostic for tumor mutation profiling to identify patients with locally advanced or metastatic non–small cell lung cancer whose tumors harbor the KRAS G12C mutation and may derive benefit from sotorasib.

The FDA has approved infigratinib for the treatment of patients with previously treated locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or rearrangement.

Artios Pharma, a company devoted to developing precision medicine–based treatments based on DNA damage response mechanisms, is entering into a global research collaboration with Novartis to develop next-generation DDR targets that will synergize with Novartis’ radioligand therapies.

Daiichi Sankyo Inc. is collaborating with Guardant Health Inc. to develop a companion diagnostic for fam-trastuzumab deruxtecan-nxki, which is being studied to treat patients with advanced metastatic HER2-mutated non‒small cell lung cancer.

Mark A. Socinski, MD, discusses the utility of circulating tumor DNA testing in lung cancer.

The FDA has granted approval to the Guardant360 CDx liquid biopsy assay as the first companion diagnostic for amivantamab-vmjw to determine which patients with locally advanced or metastatic non–small cell lung cancer harboring EGFR exon 20 insertion mutations may derive benefit from the agent after progressing on, or after, platinum-based chemotherapy.

Larotrectinib (Vitrakvi) has proved to be highly active in patients with thyroid cancer with NTRK gene fusions, exhibiting rapid and durable disease control.

Jason Niu, MD, PhD, discusses considerations for selecting between selpercatinib and pralsetinib in RET fusion–positive non–small cell lung cancer.

Mark A. Socinski, MD, discusses the evolving paradigm of targeted therapy in lung cancer.

Jose Pacheco, MD, discusses key agents that have significantly improved the care of patients with NSCLC harboring RET or NTRK fusions and efforts being made to address resistance challenges.

Helen J. Ross, MD, discusses the utility of first- and second-generation EGFR inhibitors in EGFR-mutant non–small cell lung cancer.

Frequently dysregulated in cancer cells, the PI3K pathway has long been a high-priority therapeutic target in oncology. However, initial efforts with pan–class I PI3K inhibitors were hampered by disappointing efficacy and substantial toxicity.

During this search for a breast cancer support system, my mother also investigated complementary therapies that peers had used to help cope with their fears, adverse effects, and feelings of helplessness.

The highly heterogeneous nature of cholangiocarcinoma at the genomic, epigenetic, and molecular levels has led to the development of effective new treatments for patients with these rare malignant tumors.

The cancer-specific biomarker TRIM63 was highly expressed in all classes of microphthalmia-associated transcription factor family aberration–associated renal cell carcinoma compared with other subtypes of RCC, where TRIM63 expression was low or absent.

The FDA has granted a priority review to the supplemental new drug application for ivosidenib tablets as a treatment option for patients with previously treated, IDH1-mutant cholangiocarcinoma.

Andreas Saltos, MD, discusses the importance of broad molecular testing in non–small cell lung cancer.

A higher incidence of somatically acquired genetic alterations, including damaging mutations in ZMYM3 leading to genomic instability, as well as deletions in MAP3K7, BNIP3L, RB1, and NEIL3, and gain of MYC, may lead to more aggressive prostate cancer in Black/African American men.