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WCLC 2015

GRACE Video

How Important is the Impact of Smoking Cessation on Survival?

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WCLC_2015_D_How_Important_Impact_Smoking_Cessation_Survival

 

Drs. Ben Solomon, Leora Horn, & Jack West review impressive data demonstrating a striking survival improvement from successful efforts at smoking cessation among smokers undergoing lung cancer CT screening.

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Dr. West:  Finally, there’s a fair bit — we cover a lot of ground at the World Conference on Lung Cancer, and one of the topics that I think is good to have gotten airplay is smoking cessation, and tobacco interests and policy. I was surprised, and it was sobering to see a presentation at the Presidential Symposium that suggested that smoking cessation efforts, in the process of lung cancer screening, makes a bigger interest — has a bigger impact on patient survival, not necessarily from lung cancer, but potentially from cardiovascular issues, than picking up lung cancer. Were there things about the smoking cessation discussions during this meeting that had an impact for you, or that you found particularly surprising?

Dr. Solomon:  I’m not surprised with those findings, I think smoking has a huge range of detrimental health effects, even outside lung cancer — other types of cancer, as you pointed out, cardiovascular disease as well, and I think it’s important to have strong smoking cessation measures, both at the levels of doctors and patients, but also as a society, and at a governmental level. In Australia, we’ve recently introduced plain paper packaging of cigarettes, so instead of having very attractive, different colored cigarette boxes, the government has chosen that the nastiest shade of green, sort of a puke-colored, green-brown color, to wrap cigarette packets in now. Tobacco companies are taking the government to court because they know that it will impact on sales, but I think those sorts of measures together with, as unpopular as it may be, taxes on tobacco, are things that have real impacts on smoking rates in the population, and in young people.

Dr. West:  Yeah, absolutely. It turns out the biggest impact you can have is raising taxes, especially in young smokers. Your thoughts — anything to add?

Dr. Horn:  So, I think what Australia is doing is incredible, and I remember hearing about it at the last meeting. You know, the study that they presented with smoking cessation screening — the problem is, most patients who are being screened are over age 55, so they’ve been smoking for thirty years. And so, you know, the more that we can do to stop young people from ever starting is really going to be the key to reducing smoking-related cancers.

Dr. West:  Thank you so much for joining me.

Dr. Solomon: Thanks, Jack.

Dr. Horn: Thanks, Jack!


GRACE Video

Have Your Practices Changed Regarding Prophylactic Cranial Irradiation for Extensive Stage SCLC Patients?

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WCLC_2015_23_Practices_Changed_Prophylactic_Cranial_Irradiation_Extensive_Stage_SCLC

 

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

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Dr. West:  What about patients with extensive stage small cell lung cancer who don’t have brain metastases, and complete four or six cycles of chemotherapy, and still have a good performance status? We’ve seen conflicting results on the potential value of prophylactic cranial irradiation — some suggesting a significant survival benefit, some even suggesting harm, and a greater concern, I would say, throughout cancer, and certainly lung cancer, about cognitive side effects of brain radiation. So, where does that leave you in terms of what you say to a patient who’s finishing first line therapy and still has a good performance status; Leora?

Dr. Horn:  So, I do talk to patients about the data being fairly controversial. In my clinical experience, the patients who don’t get PCI — many of them do end up with brain metastases at some point.

Dr. West:  It’s very common in small cell.

Dr. Horn:  Yeah, and so I tell them it may delay it, or if it’s not something you want to do, we don’t have to do it at this point. But, I do worry about those patients that we’re not doing PCI [for] anymore, because the Japanese studies suggested, you know, maybe we shouldn’t.

Dr. Solomon:  Yeah, so one of the things that I’ve wondered about that Japanese study, which might make it different from the Slotman study, was the Japanese patients had pretty rigorous imaging of their brain, even prior to entry onto the study, so that study, to my recollection, gave PCI to patients who didn’t have brain metastases, and I wonder whether that might be an explanation for the differences seen. So, again, we have the discussion about PCI with the concerns about neurocognitive effects, but I wonder whether an alternative in someone who doesn’t want to have PCI is to have a policy of CNS imaging — but that’s not yet supported by data, but it might be something to think about.


GRACE Video

Are There Clinically Significant Differences Among the Third Generation EGFR Inhibitors?

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Drs. Ben Solomon, Leora Horn, & Jack West compare the clinical data with the third generation EGFR TKIs so active in acquired resistance and consider whether there are significant differences between them.

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Dr. West:  We now have two, hopefully very soon, commercially available third-generation EGFR inhibitors, osimertinib, and also rociletinib. These agents really seem pretty comparable in efficacy — some differences in toxicity. What do you see as potentially clinically significant differences? If you had both available, how would you approach a patient with T790m mutation-positive acquired resistance?

Dr. Horn:  So yeah, I was going to say their similarities are in the T790m-positive patents — there are some differences in the negative patients.

Dr. West:  We’ll cover that too.

Dr. Horn:  But, I do think that — I’m going to use their numbers because they’re easier to remember than names, 9291 (osimertinib) is a little better tolerated, in my experience, than 1686 (rociletinib), the Clovis drug. I think that, for patients who are going to be on the Clovis drug, we’re going to have to be very diligent about monitoring their blood sugars because the hyperglycemia is a real toxicity that can be quite significant. Now, 9291 did have more rash, but, for these patents, they’re used to be dealing with a rash, they’ve had rashes for years because they’re been on erlotinib, gefitinib, afatinib, and even the rash of 9291 is less severe than the first and second generation agents.

Dr. West:  Clearly, these agents will do well with their marketed names, given how hard they are to differentiate based on their names now! Ben, what do you think here?

Dr. Solomon:  Yeah, look, I agree. I think they’re both very active, they both have response rates of about 50-60% in patients that have progressed on Iressa or Tarceva, but they are different in their toxicities, and rash and diarrhea with the AZD9291 compound, which we believe to be called osimertinib, today, is generally manageable and, for patients, quite similar to the rash they might have experienced, and diarrhea they might have experienced before, or even milder; whereas, hyperglycemia is a completely new toxicity and I think, again, patients need to be vigilant about this toxicity, and doctors need to know how to manage this toxicity with the use of Metformin and monitoring of blood glucose, so it can be a little bit trickier.

Dr. West:  I must say that, about a year and a half ago, when these data were first presented, I thought that managing hyperglycemia with some Metformin seemed pretty trivial for cancer patients who have an effective treatment against cancer — but when there’s an alternative that doesn’t have that, and, in some of my patents I’ve had challenging nausea and anorexia, you know, just diminished appetite, weight loss, fatigue — my experience has been that it’s not a trivial challenge, at least in a subset of patients. That said, they’re both a real advance.


GRACE Video

What Are Your Current Practices for Consolidation Chest Radiation for Extensive SCLC?

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WCLC_2015_22_Current_Practices_Consolidation_Chest_Radiation_Extensive_SCLC

 

Drs. Leora Horn, Ben Solomon, & Jack West debate whether results from a European trial of chest radiation after chemotherapy for extensive stage small cell lung cancer should lead to a change in treatment for this setting.

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Dr. West:  Not a lot here on small cell lung cancer, but there are still a couple of pretty controversial questions, including what the role is for consolidation chest radiation in patients who have residual chest disease after a good, but incomplete, response to chemotherapy. What are you guys doing in that situation? Is this something that has become a standard, or something that you often recommend, or at least discuss with patients, or is it still not something that has penetrated into common practice; Ben?

Dr. Solomon:  Yeah, so I must admit, even prior to the results with the Slotman study, which was published in the New England Journal — or, no, it was presented at ASCO — about thoracic radiation after chemotherapy, I used to worry about patients who had residual disease in their chest, because you worry that that’s a site at which they’re going to progress, and we’ve had discussions with our radiation oncology colleagues about treating that, almost preemptively. I think those data provide support to that, and provide an argument for delivering consolidation radiotherapy, if you like, for patients who have residual disease in their chest. There is additional toxicity from the treatment — the patients are pretty bashed up after their chemotherapy, so I think it’s a sort of individual discussion that we have with patients.

Dr. West:  And your thoughts?

Dr. Horn:  So, were doing the same. In the patients who tolerated chemotherapy well, and are doing well after chemotherapy, and had either bulky disease, or have residual disease, we will send them to discuss the thoracic radiation with the radiation oncology folks.


GRACE Video

Can or Will Specific Molecular Characteristics Help Determine Which ALK Inhibitor to Choose?

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WCLC_2015_20a_Specific_Molecular_Characteristics_Help_Determine_ALK_Inhibitor

 

Drs. Leora Horn, Ben Solomon, & Jack West review whether there are specific factors that should make one second generation ALK inhibitor more ideal than other competing options for a specific patient with an ALK rearrangement.

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Dr. West:  Where does this leave crizotinib — a drug that still has activity that can be long-lasting for many patients, tends to be less active, though, than any or all of these second generation ALK inhibitors, and with less activity, but not none, in the brain. So, does your view change, that you would be inclined to move these second generation inhibitors up front, if they’re paid for, or would you still favor giving crizotinib until progression, and then getting whatever you can get from a second generation inhibitor; Leora?

Dr. Horn:  So, we have trials that are going to answer that question, and it’s similar to with the EGFR front line trials, where I think the combined survival, when you’re on crizotinib, and then you get a second generation inhibitor, should be combined, compared to getting that second generation inhibitor up front. And, so, I heard this meeting, that the ALEX trial is closed, the 396 phase three trial is going to be opening, and so, we have studies that are going to answer these questions for us.

Dr. West:  But it would have to be, when we’re looking at progression-free survival, a statistically significant difference of four months, maybe enough to declare a winner as first line therapy, but that’s not the same thing as showing it’s the better strategy, compared with sequential first line crizotinib, followed by second line, second generation ALK inhibitors.

Dr. Horn:  Correct, or can we see that, you know, 50% of patients on the second generation inhibitors do not get brain metastasis? You know, that will be something that will be meaningful.

Dr. West:  And for you?

Dr. Solomon:  Yeah, no, so I think crizotinib is a great treatment, and I think there’s — we still have patients who are on the original phase one trial of crizotinib, continuing on crizotinib…

Dr. West:  You’ll retire before then!

Dr. Solomon:  That’s right, I hope! I think that is the current bar, and I think the standard first line treatment for patients with ALK rearranged lung cancer, at present, is crizotinib…

Dr. West:  Which is also, often, very well tolerated.

Dr. Horn:  Yes.

Dr. Solomon:  Yeah, and I do think the ALEX trial will be an important trial, because alectinib is another really well tolerated drug which does have better brain penetration, and I think that result will be an important result. But, again, I think we need to see how the data pans out, and I think we need to show that these drugs are better than crizotinib before moving them into first line.

Dr. West:  How would you approach a patient who is on Xalkori (crizotinib) in the first line setting, and develops two small brain metastasis that you can treat pretty readily with stereotactic radiosurgery, Gamma Knife, CyberKnife, and continue them on Xalkori, if they have no progression outside of the brain, or are you inclined to change them to a second generation ALK inhibitor with the thought that it has better penetration in the brain? Ben, why don’t I start with you?

Dr. Solomon:  Yes, so, in that particular instance, I think if the disease outside the brain was still really well controlled, and they were tolerating the crizotinib well, and my radiation oncology colleagues thought that those two lesions were suitable for stereotactic radiosurgery, I would go ahead with the stereotactic radiosurgery and continue the crizotinib. I think it would be a different situation, either if they had disease that was starting to progress outside the brain, or if they had multiple brain metastases that needed whole brain radiotherapy, and in that context, when we know that there are agents that can work in patients progressing on crizotinib, or that might work better in the brain, and therefore delay the time for them to need to have whole brain radiotherapy, that’s probably my trigger to switch.

Dr. West:  Your thoughts?

Dr. Horn:  I agree, I’d do the same.


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