GRACE :: Lung Cancer

Second Line therapy

Denise Brock

Lung Cancer Video Library – Spanish Language: Video #19 Second Line Therapy for NSCLC and ALK +

GRACE Cancer Video Library - Lung


For our 19th video in the GRACE Spanish Lung Cancer Library, Dr. Brian Hunis, Medical Director, Head and Neck Cancer Program, Memorial Cancer Institute, Miami, Florida, joined GRACE to discuss the basics of Lung Cancer for Spanish-speaking patients and caregivers.  In this video Dr. Hunis discusses second line therapy for non-small lung cell cancer patients with anaplastic lymphoma kinase (ALK) positive.






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TRANSCRIPTS – Spanish and English
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Terapia de segunda línea para pacientes con cáncer pulmonar de células no pequeñas y con la cinasa de linfoma anaplásico (CLA) positiva.

Para los pacientes que progresaron a crizotinib, en este momento hay dos fármacos: ceritinib que se puede considerar si el paciente progresa con crizotinib, y hay otro fármaco llamado alectinib que es la tercera línea para pacientes que progresan en terapia dirigida para ALK.

Lo que uno tiene que saber, es que, por la resistencia adquirida a uno de estos fármacos, uno tiene que checar la biopsia porque puede ser que el paciente no responda a estas terapias y necesite quimioterapia.

Second line therapy for non-small lung cell cancer and with anaplastic lymphoma kinase (CLA) positive

For patients that progressed to crizotinib, in this moment there are two drugs available: ceritinib that can be considered if the patient progresses with crizotinib and the other drug is alectinib which is a third line treatment for patients that progressed with ALK targeted treatment.

What we have to know is that, for acquired resistance to one of these drugs, one has to check the biopsy because the patient might not respond to these therapies and might need chemotherapy.


Immunotherapy for Previously Treated Advanced Non-Small Cell Lung Cancer

GRACE Cancer Video Library - Lung



Immune checkpoint inhibitors are now becoming approved and commercially available for patients with previously treated advanced NSCLC. Dr. Eddie Garon, medical oncologist at UCLA, summarizes key data and explains their current role in treatment.

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So, the initial studies of checkpoint inhibitors have been in patients who have been previously treated, and one of the reasons for that is that has been, typically, a difficult clinical scenario. We have been able to be somewhat effective, certainly with chemotherapy, and there are many people who do quite well for a long period of time with chemotherapy in the front-line setting. But, unfortunately, that’s much less common in the second-line setting — most patients, for instance, with mutations in EGFR or ALK now are receiving inhibitors of those in the front-line setting, so when you take, for instance, patients who do not have mutations in those genes and look at them in a second-line setting, we generally have anticipated that about 10% of them would have, what we would call, a clinical response to chemotherapy, and that that response is generally not of the sort of duration we would want. So, it was an excellent opportunity when the checkpoint inhibitors became available, to test whether or not they could lead to superior outcomes than, for instance, docetaxel or Taxotere. Taxotere has been a standard drug that has been used for many years in this setting, and can be effective, but is less effective than we would want, and is associated, certainly, with some toxicity.

So, the phase 1 study looking at Opdivo, for instance, looked at that group of patients, and then — I was involved with a very large phase 1 study where we actually treated, it was 495 patients total, and about 400 of those patients were previously treated, so they had received prior therapy, and there you saw somewhere near 1 in 5 patients responding to the drug, and when they  responded, they responded for a long period of time. But, that data, although a large data set, was not compared to standard therapy, so it’s important to evaluate what would happen if you compared a checkpoint inhibitor, for instance, to standard therapy, because that’s what you’re going to have to be deciding in the clinic, is whether or not you want to use one of these kinds of drugs or if you want to use a drug like Taxotere.

So, the first data sets, now, are available in that setting, and the first one to read out was the CheckMate 017 study, this was of the drug Opdivo, and this took patients with squamous cell carcinoma, one type of non-small cell lung cancer, and randomized them to receive either Opdivo or Taxotere. The results were, from a clinical trial perspective, very clear — that patients benefitted if they received Opdivo. Of course, not every patient benefitted, but when you looked at the outcomes and how the patients responded to the drug, how long people were able to stay on the drug, how long people survived, clearly it was in favor of Opdivo, and Opdivo is now approved in squamous cell carcinoma of the lung.

CheckMate 057 looked at non-squamous, non-small cell lung cancer — there, again, compared to Taxotere. It, again, led to improvements in clinical outcomes, and, so, that was certainly very exciting. That is, in the CheckMate 057 data, their biomarker, the degree of expression of PD-L1, was very closely associated with the response to Opdivo, and I’ll discuss the biomarker in a separate session. Then there was also a set of data presented with atezolizumab, which is a PD-L1 inhibitor — that, again, was randomized versus Taxotere, and, in that study, when one looks at outcomes like survival, for instance, in patients who had some degree of staining for PD-L1, there were clearly statistically significant improvements in response versus Taxotere, and it appeared that, like the CheckMate 057 data, that responses tended to be significantly more common, and clinical outcomes tend to be improved, relative to Taxotere, more specifically in patients who had a greater degree of staining for PD-L1.

Dr West

What is the value of maintenance therapy in advanced NSCLC, and who should get it?


We’ve covered the question of maintenance therapy for lung cancer in many posts over the past 5-6 years as it has evolved from a concept with little evidence to a standard of care, but it is difficult to get a good summary of the big picture. This presentation is my attempt to distill the field into the most important principles.


What is the value of maintenance therapy in advanced NSCLC, and who should get it? from H. Jack West

And for those who want to download the slides in an easily printable form, here’s the slide set as a pdf file: Maintenance therapy primer

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Dr West

Second Line Chemo or Tarceva: Which is Better for Advanced NSCLC Patients without an EGFR Mutation?


Dr. Mark Socinski covered the TAILOR trial, an Italian study directly comparing second line Taxotere (docetaxel) to Tarceva (erlotinib) in advanced NSCLC patients without an EGFR mutation, in the ASCO Lung Cancer Highlights program.  However, as a preview to his comments you’ll find in the podcast here, I’ll share that he wasn’t fond of the trial or the questionable value of the results from it.  

Still, the trial is among the ones likely to be most discussed in the field of lung cancer from ASCO 2012, so it’s worth hearing what it showed, along with an expert perspective of how to interpret it.  Below, you’ll find the audio and video versions of the podcast along with the transcript and figures.

Dr. Socinski ASCO LC Highlights 2012 TAILOR Trial Audio Podcast

Dr. Socinski ASCO LC Highlights 2012 TAILOR Trial Transcript

Dr. Socinski ASCO LC Highlights 2012 TAILOR Trial Figs

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Dr West

TITAN Trial: Comparison of Chemo and Tarceva in Patients Who Progressed Early on First Line Chemo for Advanced NSCLC


One of the trials presented at the Chicago Multidisciplinary Symposium in Thoracic Oncology last month was the TITAN trial, one of a pair of studies conducted in Europe to test the oral EGFR inhibitor Tarceva (erlotinib) in patients with chemotherapy pre-treated advanced NSCLC. The other trial, SATURN, was designed to test Tarceva as a maintenance therapy vs. placebo in patients who had shown a response or stable disease after four cycles of first line chemotherapy (without the VEGF inhibitor Avastin (bevacizumab)) has been summarized previously and ultimately led to the approval of Tarceva as a maintenance therapy in this patient population. But what happened to the significant fraction of patients who progressed by the time of the repeat imaging after four cycles of first line platinum-based doublet chemotherapy? They were directed to the TITAN trial, which was a head to head comparison of Tarceva vs. either Taxotere (docetaxel) or Alimta (pemetrexed), both well studied and commonly used second line agents for advanced NSCLC. The trial looked for an improvement in overall survival with Tarceva.

patient-distribution-on-saturn-vs-titan-trials (click on image to enlarge)

The trial closed earlier than planned, due to slow enrollment, with just 424 patients, which leaves it quite underpowered to detect a difference even if there really is one between the two treatment approach. Still, there may be some conclusions that can be drawn from what they saw, even if limited by smaller numbers than needed to say anything definitive.

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