Corey J. Langer, MD, is the director of Thoracic Oncology at Penn Medicine; as well as a professor of medicine (hematology-oncology) at the Hospital of the University of Pennsylvania at the Perelman School of Medicine

Corey J. Langer, MD, Professor of Medicine, Hematology/Oncology Division, University of Pennsylvania, Abramson Cancer Center, discusses the standard treatment paradigm for patients with locally advanced non-small cell lung cancer (NSCLC). 

In general, Langer notes that these patients generally have a good prognosis. Their performance status is intact and they have less than a 5-10% loss in weight from baseline. If the tumor is unresectable, the standard of care is concurrent radiation therapy and chemotherapy, likely etoposide plus cisplatin or paclitaxel and carboplatin. Trials have investigated adding induction or consolidation therapy but none have shown any additional benefits. 

Treating locally advanced NSCLC is counter-intuitive to other paradigms, Langer notes. For instance, in the adjuvant setting it is common to give four cycles of systemic chemotherapy, but in the locally advanced setting, where the disease burden is worse, an added benefit has not been observed from providing four or more cycles. 

The addition of targeted therapies to concurrent radiation and chemotherapy has also failed to show a benefit. Trials looking at the addition of bevacizumab resulted in undue toxicities and the addition of tyrosine kinase inhibitors provided unclear results. Further trials are currently ongoing looking at vaccines and the EGFR antibody cetuximab.

Videos

Dr. Corey Langer, from the University of Pennsylvania, Abramson Cancer Center, Discusses Treating Locally Advanced Non-small Cell Lung Cancer.

Dr. Langer Discusses Treating Locally Advanced NSCLC

Corey J. Langer, MD, Professor of Medicine, Director, Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, explains the PARAMOUNT study, which initially consisted of 939 patients with advanced nonsquamous non—small cell lung cancer (NSCLC) that were first given 4 courses of first-line pemetrexed (Alimta) and cisplatin. The 539 patients from the initial group that did not demonstrate disease progression were randomized into two arms, one receiving maintenance pemetrexed and the other receiving a placebo. Read more about the trial >>> 

Pemetrexed Maintenance Improves Progression-Free Survival in Patients With NSCLC

The trial adequately justified that continuation maintenance with pemetrexed improves progression-free survival (PFS) in patients who received pemetrexed as part of their initial chemotherapy regimen.

Langer remains unconvinced of the drug's efficacy because an overall survival (OS) benefit was not shown. If the PFS does not translate into OS then consideration needs to be taken as to whether the benefits outweigh the toxicity.

The main concern Langer voices regarding this trial is similar to his concern for the JMEN trial that also studied maintenance pemetrexed. (

Dr. Langer Discusses the JMEN Maintenance Pemetrexed Trial 

) The main criticism of this trial was the mandatory crossover from the control arm to the pemetrexed arm.

Dr. Corey Langer from the Abramson Cancer Center Discusses the PARAMOUNT Study

Dr. Langer Discusses the PARAMOUNT Study

Corey J. Langer, MD, Professor of Medicine, Director, Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, explains that as a clinician he does not use cost as a decision factor. The care of the patient and their quality-of-life takes priority over the cost efficacy of a drug. The cost analysis should not be a determining factor for which therapeutic agent to give.

Dr. Corey Langer from Abramson Cancer Center on Cost Analysis in the Treatment Decision

Dr. Langer on Cost Analysis in the Treatment Decision

Corey J. Langer, MD, Professor of Medicine, Director, Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, discusses the design and major criticisms of the JMEN phase III trial.

JMEN was a randomized trial looking at maintenance pemetrexed in advanced or metastatic (stage IIIB and IV) non-small-cell lung cancer. The trial examined patients that had been treated with platinum-based first-line chemotherapy and were stable or had not progressed. JMEN demonstrated a significant survival benefit and was heralded as a paradigm changing trial.

The largest criticism of the trial was the absence of a mandatory crossover from the control arm to intravenous pemetrexed. 67% of patients on the placebo arm received a second-line therapy, of this amount only 19% received pemetrexed, the remaining 81% received an EGFR TKI or docetaxel.

Langer believes that receiving second-line pemetrexed alone should have been built into the trial. If this had happened the trial could have prevented major criticism.

Dr. Corey J. Langer from Abramson Cancer Center Discusses the JMEN Maintenance Pemetrexed Trial

Dr. Langer Discusses the JMEN Maintenance Pemetrexed Trial

Corey J. Langer, MD, Professor of Medicine, Director, Thoracic Oncology, Abramson Cancer Center, University of Pennsylvania, explains the importance of assessing the patient populations in clinical trials. If the population is not representative of the patients you see in your practice it may not be relevant to you.

The demographics of the patients entered into a trial may have a direct bearing on the outcome. As an example Langer uses a study by Chandra Belani, MD, which examined continuation maintenance therapy using gemcitabine and carboplatin.

The population of this trial contained somewhat older patients with a marginal performance status (PS) of 2. This trial did not show an improvement in progression-free survival or overall survival and closed earlier than planned, unlike other similar trials. It is suggested that the higher PS of the patients enrolled had a negative effect on the outcome of the trial.

Dr. Corey J. Langer from Abramson Cancer Center on Assessing Patient Populations in Clinical Trials

Corey J. Langer, MD

Articles

Dr. Langer Discusses Treating Locally Advanced NSCLC

Dr. Langer Discusses the PARAMOUNT Study

Dr. Langer on Cost Analysis in the Treatment Decision

Dr. Langer Discusses the JMEN Maintenance Pemetrexed Trial

Dr. Langer on Assessing Patient Populations in Trials