Heather A. Wakelee, MD, medical oncologist, thoracic specialist, professor of medicine at Stanford University Medical Center, discusses therapy options when patients with lung cancer must receive treatment options immediately rather than wait for molecular testing results.

In newly diagnosed patients, when considering therapies and how long they can wait before receiving treatment, the physical factors of the disease must be considered, explains Wakelee. Some patients, by the time they physically present, are very ill with tumor burden, have painful bone metastases, liver metastases, or difficulty breathing. Patients who are symptomatic may not be able to wait for their mutational test results before receiving treatment, says Wakelee.

Patients who must have treatment immediately after diagnosis and may have a high chance of having a driver mutation can receive chemotherapy and maybe bevacizumab (Avastin), but not immunotherapy, according to Wakelee. Patients with driver mutations may react poorly to immunotherapy, further delaying their targeted treatment, she says.

Meanwhile, patients who are unlikely to have driver mutations can receive chemotherapy plus immunotherapy, Wakelee says. In some cases, payers will not cover chemoimmunotherapy until the patient is confirmed to have no driver mutation. In that situation, patients can always receive chemotherapy, which may not be ideal, but is never a wrong choice, concludes Wakelee.

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Heather A. Wakelee, MD, discusses therapy options when patients with lung cancer must receive treatment options immediately rather than wait for molecular testing results.

Dr. Wakelee on Immediate Therapy Options in Lung Cancer

Heather A. Wakelee, MD, medical oncologist, thoracic specialist, professor of medicine at Stanford University, discusses results from the phase III IMpower150 trial in non—small cell lung cancer (NSCLC).

In the phase III IMpower150 trial, patients with metastatic disease were randomly assigned 1:1:1 to receive either atezolizumab (Tecentriq) plus bevacizumab (Avastin) and carboplatin/paclitaxel (ABCP); atezolizumab plus carboplatin/paclitaxel (ACP); or bevacizumab plus carboplatin/paclitaxel (BCP). This trial is the first to combine antiangiogenic agents with immunotherapy, says Wakelee. Results showed improved progression-free survival and overall survival (OS) with the four-drug regimen in all-comers, but also in those with 

 mutations. Although the OS benefit wasn’t statistically significant in those patients, it was impressive, she adds.

Wakelee believes more studies investigating the role of antiangiogenic agents in combination with chemotherapy and immunotherapy are needed. Potential areas for further research include combination of antiangiogenic agents with different chemotherapies, further exploration into bevacizumab and ramucirumab (Cyramza) and their role in the treatment of this patient subset, and the addition or removal of VEGF inhibitors with antiangiogenic agents, concludes Wakelee.

Heather A. Wakelee, MD, medical oncologist, thoracic specialist, professor of medicine at Stanford University, discusses results from the phase III IMpower150 trial in non–small cell lung cancer.

Dr. Wakelee on First Trial to Combine Antiangiogenic Agents With Immunotherapy in NSCLC

Heather A. Wakelee, MD, professor of medicine (oncology), Stanford University Medical Center, discusses the rationale to explore osimertinib (Tagrisso) in combination with concurrent chemotherapy in patient with 

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

-mutant NSCLC will develop resistance to osimertinib. In approximately 5% to 10% of those cases, the EGFR TKI is still suppressing the cancer cells. If the TKI is stopped, it will lead to rapid growth of those cancer cells. These patients can easily be identified because they will become symptomatic within days of stopping the drug. For this subset, continuing the EGFR TKI along with the chemotherapy could be a potential strategy in practice.

Conversely, patients could have good control of their brain disease but begin to progress in the body. In practice, those patients are typically continued on osimertinib and given chemotherapy to control that progression. At the 2019 ASCO Annual Meeting, Wakelee presented a poster showing that the combination of osimertinib and chemotherapy is fairly safe. These data are not enough to warrant its use in routine practice, but it provides a foundation for further exploration, concludes Wakelee.

Heather A. Wakelee, MD, professor of medicine, Stanford University Medical Center, discusses the rationale to explore osimertinib (Tagrisso) in combination with concurrent chemotherapy in patient with EGFR-mutant non–small cell lung cancer.

Dr. Wakelee on Rationale to Explore Osimertinib With Concurrent Chemotherapy in EGFR-Mutant NSCLC

Heather A. Wakelee, MD, professor of medicine (oncology), Stanford University Medical Center, discusses osimertinib (Tagrisso) and its role in treating patients with 

Osimertinib is the only FDA-approved third-generation EGFR TKI. Initially, it was indicated for patients who had already been treated with a first- or second-generation drug and had the acquired resistance mutation T790M. In this setting, osimertinib elicited a 60% to 70% response rate and responses can last ≥1 year in select patients, according to Wakelee.

The FLAURA study examined osimertinib in the first-line setting. In the trial, patients with EGFR mutation-positive NSCLC received either osimertinib or standard EGFR TKI, which was gefitinib (Iressa) or erlotinib (Tarceva). Results showed that the median progression-free survival of 19 months. Osimertinib has become the standard first-line therapy in the United States for this patient population, according to Wakelee. It is a well-tolerated agent, but physicians must be mindful of its unique toxicities, including neutropenia, thrombocytopenia, and QT prolongation, Wakelee explains, adding that she recommends physicians check lab reports and electrocardiogram, especially early on.

Heather A. Wakelee, MD, professor of medicine (oncology), Stanford University Medical Center, discusses osimertinib and its role in treating patients with EGFR-mutant non–small cell lung cancer.

Dr. Wakelee on Advances in EGFR-Mutant NSCLC Treatment

Heather A. Wakelee, MD, associate professor of Medicine (Oncology), Stanford University Medical Center, regent, International Association for the Study of Lung Cancer (IASLC) discusses the FDA approval of pembrolizumab (Keytruda) in the frontline setting for patients with non—small cell lung cancer (NSCLC).

Heather A. Wakelee, MD, associate professor of Medicine (Oncology), Stanford University Medical Center, regent, International Association for the Study of Lung Cancer (IASLC) discusses the FDA approval of pembrolizumab (Keytruda) in the frontline setting for patients with non–small cell lung cancer (NSCLC).

Dr. Wakelee on FDA Approval of Frontline Pembrolizumab in NSCLC

Heather A. Wakelee, MD, associate professor of Medicine (Oncology), Stanford University Medical Center, regent, International Association for the Study of Lung Cancer (IASLC) discusses updated efficacy findings from the BIRCH trial, which was a phase II study of atezolizumab (Tecentriq) for patients with PD-L1—selected advanced non–small cell lung cancer (NSCLC). Wakelee discussed these findings during an interview at the 2016 IASLC Multidisciplinary Symposium on Thoracic Oncology.

The updated results of the BIRCH study demonstrate a median overall survival of 12 months. In the first-line cohort all comers with an immunohistochemistry score of TC1/2/3 had a median survival of over 20 months. In patients who had higher PD-L1 expression, the median survival has not yet been reached, Wakelee explains.

Additional studies are exploring atezolizumab in other settings and in combination. The IMpower-110 trial is a randomized study in selected patients looking at atezolizumab compared with chemotherapy in the first-line setting, she says. The OAK study is a randomized phase III trial comparing atezolizumab with docetaxel in unselected patients in the second-line setting.

Heather A. Wakelee, MD, associate professor of Medicine (Oncology), Stanford University Medical Center, regent, International Association for the Study of Lung Cancer (IASLC) discusses updated efficacy findings from the BIRCH trial, which was a phase II study of atezolizumab (Tecentriq) for patients with PD-L1–selected advanced non–small cell lung cancer (NSCLC). Wakelee discussed these findings during an interview at the 2016 IASLC Multidisciplinary Symposium on Thoracic Oncology.

Heather A. Wakelee, MD, FASCO

Articles

Dr. Wakelee on Immediate Therapy Options in Lung Cancer

Dr. Wakelee on First Trial to Combine Antiangiogenic Agents With Immunotherapy in NSCLC

Dr. Wakelee on Rationale to Explore Osimertinib With Concurrent Chemotherapy in EGFR-Mutant NSCLC

Dr. Wakelee on Advances in EGFR-Mutant NSCLC Treatment

Dr. Wakelee on FDA Approval of Frontline Pembrolizumab in NSCLC

Dr. Wakelee on BIRCH Trial for Atezolizumab in Patients With NSCLC