LUNG CANCER

Broad adoption of testing methods that allow for assessing all possible actionable targets and diagnostic markers in advanced cancer is becoming more complex with greater availability of lifesaving targeted therapies.

"Taletrectinib is a promising oral tyrosine kinase inhibitor highly selective for ROS1/NTRK mutations with potent activity against ROS1 resistance mutations like G2032R."

Suresh Ramalingam, MD, FASCO, discusses the key takeaways regarding the toxicities observed in the phase 3 CheckMate 227 clinical trial, which evaluated immunotherapeutic agents nivolumab plus ipilimumab as treatment of patients with non–small cell lung cancer.

"This interim clinical and translational data add further confidence to the potential patient benefit of selective AXL inhibition with bemcentinib, to reverse resistance to immune checkpoint inhibitors in selected cAXL-positive patients who have relapsed on immunotherapy."

"In the case of sarcomas treated with the current standard of care, doxorubicin, tumors may be initially responsive in their primary location, but become unresponsive after metastasis to the lungs, which eventually becomes the most likely cause of patients' death."

In an interview with Targeted Oncology, Suresh Ramalingam, MD, FASCO, discussed the findings from the CheckMate 227 study that support the FDA’s approval of the combination of nivolumab and ipilimumab in patients with advanced NSCLC.

Community physician Jason Williams, MD, DABR, talks to academic oncologist George R. Simon, MD, FACO, FCCP, for an episode of Targeted Talks.

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.

In an interview with Targeted Oncology, Robert M. Jotte, MD, PhD, discussed the results of the exploratory analysis of patients with NSCLC from the IMpower150 who had bulky disease.

"Selpercatinib had marked intracranial anti-tumor activity in RET fusion–positive patients with [NSCLC and] CNS metastases. Tumor responses were durable, independently confirmed, and observed in patients with prior systemic chemotherapy."

"The ARROW trial results presented today during the ASCO virtual meeting showed that patients with RET fusion–positive lung cancer treated with the selective RET inhibitor pralsetinib had durable responses. In addition to supporting the development of pralsetinib across a broad population, these data highlight the urgency to test [patients with] lung cancer with next-generation sequencing so that eligible patients may be identified for treatment."

Patients with ALK-positive non–small cell lung cancer showed clinically meaningful improvement in overall survival when receiving alectinib, a highly selective second-generation TKI, versus those treated with crizotinib, according to updated data from the pivotal phase 3 ALEX trial presented at the 2020 ASCO Virtual Scientific Program.

Durable clinical activity was demonstrated with tepotinib, an oral, highly selective MET inhibitor, in patients with locally advanced or metastatic non–small cell lung cancer and a MET exon 14 skipping mutation identified through liquid or tissue biopsy. This data was from the phase 2 VISION trial presented during the at the 2020 Virtual Scientific Meeting and published in the New England Journal of Medicine.

Phase 3 BGB-A317-307 trial results showed statistically significant improvements in progression-free survival with tislelizumab plus chemotherapy versus chemotherapy alone in Chinese patients with untreated advanced squamous non–small cell lung cancer.

“Importantly, the separation among the curves seems to be observed over time and, indeed, survival at 2 years improves from 14% [of participants] in the control arm to 22% on the experimental arm. The magnitude of the benefit is very similar and very consistent across all the prespecified subgroups of patients analyzed, including those treated with cisplatin or those patients with liver or brain metastases.”

The FDA has approved ramucirumab in combination with erlotinib for the first-line treatment of patients with metastatic non–small cell lung cancer harboring EGFR exon 19 deletions or exon 21 mutations.

Mark M. Awad, MD, PhD, discusses the characterization of patients with non–small cell lung cancer who have MET exon 14 skipping alterations and potential acquired resistance mechanisms.

"CheckMate 9LA met its primary end point of overall survival at the pre-planned interim analysis…With early separation of overall survival curves and lower progressive disease rates as best overall response, the hypothesis for this study design was validated."

Modest survival benefits were observed in patients with extensive-stage small cell lung cancer who received the combination of pembrolizumab and etoposide plus platinum compared with patients who received EP and placebo. Although progression-free survival rates reached the threshold for significance, overall survival rates failed to reach the prespecified threshold, according to data from the phase 3 KEYNOTE-604 trial.

"Based on these results, we note that the combination of nivolumab and ipilimumab, which is now approved by the United States FDA, is a novel chemotherapy-sparing first-line treatment approach for advanced-stage non-small-cell lung cancer."

"Trastuzumab deruxtecan demonstrated clinical activity in this interim analysis, with a high ORR and durable response rate in a heavily pretreated population of patients with HER2-mutated NSCLC."

Frontline treatment with the TIGIT inhibitor tiragolumab plus atezolizumab demonstrated greater efficacy versus single-agent checkpoint inhibitor therapy in locally advanced or metastatic non–small cell lung cancer, according to results of the phase 2 CITYSCAPE trial reported at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

"Prior administration of chemotherapy is associated with increased risk of death [from COVID-19] while immunotherapy and tyrosine kinase inhibitors are not."