Biomarker-Driven Lung Cancer

FDA approvals of novel agents for molecularly defined subtypes of non–small cell lung cancer are poised to change both patient outcomes as well as pretreatment testing requirements for those harboring these tumors.

A New Drug Application was submitted to the FDA seeking approval of the investigational KRAS G12C inhibitor sotorasib as treatment of patients with KRAS G12C-mutated locally advanced or metastatic non–small cell lung cancer, as determined by an FDA-approved test, following at least 1 prior systemic therapy.

Alexander Spira, MD, PhD, discusses how he chooses treatment for patients with lung cancer.

The FDA granted a Breakthrough Therapy designation to sotorasib for the treatment of patients with locally advanced or metastatic non–small cell lung cancer who harbored a KRAS G12C mutation following at least 1 prior line of systemic therapy.

Treatment with lorlatinib induced a 72% reduction in the risk of progression or death compared with crizotinib in patients with previously untreated ALK-positive advanced non–small cell lung cancer.

In an interview with Targeted Oncology, Alexander Spira, MD, PhD, discussed the role of identifying biomarkers in patients with lung cancer based on the vast amount of data and significant number of approved therapies available for biomarker-driven disease.

Benjamin Solomon, MBBS, PhD, discusses the intracranial responses observed in the CROWN trial of lorlatinib versus crizotinib in patients with ALK-positive non–small cell lung cancer.

Lyudmila Bazhenova, MD, led a peer discussion about the frontline treatment options for a middle-aged male patient with ALK-positive non–small cell lung cancer.

Adagrasib demonstrated promising antitumor activity as monotherapy in patients with previously treated KRAS G12C–mutant non–small cell lung cancer, according to findings from the phase 1/2 KRYSTAL-1 trial.

Driver alterations in neuregulin 1 fusions have recently come to light as a new target in patients with advanced or metastatic solid tumors. Multiple factors contribute to poor outcomes in this patients population with limited option for resolution.

Vivek Subbiah, MD, discusses how the data from selpercatinib have generated excitement for precision medicine in the treatment landscape for patients with RET-driven lung cancer.

Topline results from the phase 2 CodeBreaK 100 clinical trial were consistent with phase 1 data, withthe KRAS inhibitor sotorasib having achieved a satisfactory objective response rate when administered as treatment of patients with KRAS G12C–mutant non–small cell lung cancer, who had failed a median of 2 prior lines of anti-cancer therapies, which could include immunotherapy and/or chemotherapy.

Selpercatinib-related hypersensitivity reactions occurred infrequently in patients with RET fusion-positive non–small cell lung cancer, with more cases reported in patients previously treated with an immune checkpoint inhibitor, but reactions were deemed manageable with recommended guidance and supportive care.

In an interview with Targeted Oncology, Anthony P. Conley, MD, discussed findings from an analysis of the efficacy and safety of entrectinib in patients with non-small cell lung cancer harboring a ROS1 or TRK fusion.

In patients with non–small cell lung cancer harboring a KRAS G12C mutation, an aberration without any FDA approved treatment options, a study showed that the investigation agent, sotorasib achieved encouraging antitumor activity.

"We believe that poziotinib is a significant advancement for patients with this deadly disease in an area of high unmet medical need."

In a single-arm phase 2 clinical trial, pyrotinib had promising antitumor activity as treatment of patients with HER2-positive non–small cell lung cancer.

The NCCN guidelines recommend biomarker testing as a part of the pathologic evaluation for patients with non-squamous advanced NSCLC and NCC set out to determine how these guidelines decrease the incidence of mortality.

Brain metastasis responses were elicited from treatment with pembrolizumab in patients with non–small cell lung cancer, in a PD-L1–positive cohort of a phase II clinical trial conducted by researchers at Yale Cancer Center. According to a YCC press release, pembrolizumab prolonged overall survival with limited toxicity in these patients.

The FDA has provided clearance to an Investigational New Drug application for GT103 for the treatment of solid tumors. A phase I clinical trial will be initiated to evaluate this novel targeted immunotherapy in patients with refractory non–small cell lung cancer, announced Grid Therapeutics, LLC.

The combination of tislelizumab, a PD-L1 antibody, pemetrexed and platinum-based chemotherapy achieved a statistically significant prolongation in progression-free survival compared with pemetrexed and platinum chemotherapy alone as first-line treatment of patients with nonsquamous non–small cell lung cancer, meeting the primary end point of a phase III BGB-A317-304 trial.

A 69-Year Old Man With Metastatic BRAF V600E-Mutated Metastatic NSCLC

Luis E. Raez, MD, discusses targeted therapies for patients with lung cancer who have genetic alterations.

The FDA has accepted the Biologics License Application for and granted Priority Review to the combination of nivolumab plus ipilimumab with limited chemotherapy as a first-line treatment of patients with metastatic or recurrent non–small cell lung cancer who have no EGFR or ALK genomic tumor aberrations, according to a press release from Bristol Myers Squibb. The Prescription Drug Free User Act target action date is set as August 6, 2020, and the combination was granted Fast Track designation.

In an interview with Targeted Oncology, James A. Reeves, MD, discussed how targeted therapies are being used presently in lung cancer and the potential of these agents in the future.

The FDA has accepted and granted a priority review to a supplemental Biologics License Application for pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high who have progressed following prior treatment and who have no satisfactory alternative treatment options.

Nathan A. Pennell, MD, PhD, discusses the role of molecular testing when treating and managing patients with&nbsp;<a>lung cancer.</a>&nbsp;He shares his advice on what to do for patients who need therapy immediately, as well.

The immunotherapeutic vaccine OSE-2101 demonstrated a favorable 12-month survival rate as second- or third-line treatment of patients with HLA-A2-positive advanced non&ndash;small cell lung cancer, meeting the primary end point of overall survival in the phase III Atalante 1 study, according to a press release from the drug developer, OSE Immunotherapeutics, Inc.

A rolling New Drug Application has been submitted for pralsetinib as treatment of patients with RET fusion–positive non–small cell lung cancer, according to a press release from Blueprint Medicines Corporation.

An association was found between a lower risk of grade 3 or higher chemotherapy toxicity with higher body mass indexes and normal albumin, a protein made in the liver, levels in older adult patients with solid tumors, according to an analysis of a prospective, multicenter study.