Dr Rotow on Challenges With Targeting CNS Metastases in Lung Cancer

Julia Rotow, MD, clinical director, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses existing unmet needs for patients with lung cancer and central nervous system (CNS) metastases, as well as the importance of multidisciplinary collaboration throughout all aspects of cancer care.

The lung cancer field’s understanding of the efficacy of both established and novel agents in patients with lung cancer and CNS involvement remains limited, necessitating prospective clinical trials that may elucidate CNS-specific responses, Rotow begins. Although the mechanism of the blood-brain barrier is well understood, the blood-tumor barrier may be even more permeable, she notes. Recent data indicate that the blood-tumor barrier may allow for therapeutic responses in the CNS that are comparable to those observed systemically with agents that are not typically considered to have CNS activity, Rotow explains.

The field’s grasp on the mechanisms of resistance to current therapies in the CNS is still in its infancy, according to Rotow. However, this area of research is challenging to study because CNS biopsies are not possible and plasma-derived circulating tumor DNA is unlikely to reliably detect genomic profiles in the CNS, Rotow says. Emerging cerebrospinal fluid–based DNA profiling technologies may offer less invasive alternatives for studying CNS genomics, although their clinical utility requires further investigation, Rotow emphasizes.

Furthermore, the complexity of lung cancer treatments, including the integration of neoadjuvant, perioperative, and adjuvant regimens into the paradigm, underscores the necessity of multidisciplinary collaboration early in each patient’s disease course, Rotow reports. Surgeons, medical oncologists, and radiation oncologists should all be present during treatment decision-making conversations, according to Rotow. Although this multidisciplinary approach is well established in many academic centers, it needs to be effectively facilitated in community oncology settings to ensure that all patients with lung cancer receive comprehensive care from the outset, Rotow concludes.

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Julia Rotow, MD, discusses existing unmet needs for patients with lung cancer and CNS metastases.

Julia K. Rotow, MD, medical oncologist, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, discusses the results of an ongoing phase 1/2 trial evaluating the safety and efficacy of osimertinib (Tagrisso) in combination with gefitinib (Iressa) as a first-line treatment for patients with stage IV 

-mutant non—small cell lung cancer (NSCLC).

The dose-escalation phase of this study confirmed that 80 mg of osimertinib plus 250 mg of gefitinib once daily was the maximum-tolerated dose, says Rotow.

Although the trial is ongoing, initial safety findings suggest that the combination is well tolerated, says Rotow. A feasibility analysis demonstrated that 81.5% of patients completed at least 6 cycles of combination therapy.

The overall response rate was 85.2% (95% CI, 67.5-94.1), with 14.8% of patients experiencing stable disease. These findings are comparable with osimertinib monotherapy; however, these data are not fully matured as enrollment is ongoing, explains Rotow.

Once the data have fully matured, progression-free survival will be an important end point to evaluate as it may determine whether the potential clinical benefit of the combination regimen outweighs the added toxicity, concludes Rotow.

Julia K. Rotow, MD, discusses the results of an ongoing phase 1/2 trial evaluating the safety and efficacy of osimertinib in combination with gefitinib as a first-line treatment for patients with stage IV EGFR-mutant non–small cell lung cancer.

Julia K. Rotow, MD

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Dr Rotow on Challenges With Targeting CNS Metastases in Lung Cancer

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