nkmiami

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MMS: Error

click on mms: error for link to nejm
tripling of PFS in stage III NSLC, obviously OS will take some time.

should we even be wasting our time with the RTOG adjuvant trial of opdivo

MMS: Error
 
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scarbrtj

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Can't wait to say "Can you be more PACIFIC please" when next med onc colleague asks whether we should consider additional therapy after chemoRT for Stage III NSCLC...
 

medgator

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MMS: Error

click on mms: error for link to nejm
tripling of PFS in stage III NSLC, obviously OS will take some time.

should we even be wasting our time with the RTOG adjuvant trial of opdivo

MMS: Error
Never hurts to have competition in the six figure drug space
 
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nkmiami

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Every end-point positive except the most important one - survival.

So the patient asks the Medical Oncologist, "Doctor, if I take this drug will it make me live longer?"

Answer [bunch of Star Trek techno babble] = "NO"
You can bank on os becoming positive with those numbers and no crossover.
 
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medgator

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I don't get it. It's a win for patients and they're still receiving XRT.
Because medicine doesn't exist in a bubble? All of these PD drugs are essentially six figure treatments for life, at some point, the elephant in the room needs to be addressed.

And keep in mind the "curative" XRT course costs less than the adjuvant pd inhibitor that improves PFS

Hence my response to the original comment:

should we even be wasting our time with the RTOG adjuvant trial of opdivo
It's better to have two approved drugs than one....competition lowers price
 
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nkmiami

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I think there is a suggestion of a possible synergy between the drug and radiation, that hopefully will be seen in other tumors. Radiation here seemed to make up for low PDL1 expression. In stage 4 NSCLC, (and stage III have subclinical mets 80% of time), trials show that the major benefit of these agents are in tumors that have high expression of PDL1. OPDIVO did not show a PFS benefit in the first line setting in unselected stage 4 pts, let alone, one 3x the control arm.
A phase III trial of frontline durvalumab (in combination with an yervoy analog) was negative for PFS in stage IV NScLC.

Plus, the drug is a relative bargain: compared to the 475,000 $ for leukemia

New Gene-Therapy Treatments Will Carry Whopping Price Tags
 
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Gfunk6

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Everything is a bargain relative to something else. That misses the point.

Medicare (CMS) has made it abundantly clear that the cost curve for medical care and especially oncology needs to be bent. It is very clear that they are not going to "grow a pair" and confront pharma with cost controls. Therefore, they are focusing all of their attention on physicians. Rather than reducing the cost of drugs, they are "encouraging" oncologists to prescribe less expensive treatments. Enforcement will come through mutual gain/pain; in other words, if you save Medicare money they will share cost savings with you, if you go over the limit then you eat the excess.

Looking at our practice and others (as medgator alludes to above) radiation is actually highly cost efficient and clinically effective. However, the gatekeepers of all things financial will be Medical Oncologists, not Radiation Oncologists. Therefore, unless you are in a well-integrated group, Rad Oncs run the risk of seeing fewer patients for more expensive and less effective immunotherapies for the sake of cost containment ("penny-wise, pound foolish.")

This is the reality of private practice today and which is why I (and others) automatically do not jump with joy whenever a new trial is published with a super expensive drug with marginal benefit.
 
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nkmiami

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Everything is a bargain relative to something else. That misses the point.

Medicare (CMS) has made it abundantly clear that the cost curve for medical care and especially oncology needs to be bent. It is very clear that they are not going to "grow a pair" and confront pharma with cost controls. Therefore, they are focusing all of their attention on physicians. Rather than reducing the cost of drugs, they are "encouraging" oncologists to prescribe less expensive treatments. Enforcement will come through mutual gain/pain; in other words, if you save Medicare money they will share cost savings with you, if you go over the limit then you eat the excess.

Looking at our practice and others (as medgator alludes to above) radiation is actually highly cost efficient and clinically effective. However, the gatekeepers of all things financial will be Medical Oncologists, not Radiation Oncologists. Therefore, unless you are in a well-integrated group, Rad Oncs run the risk of seeing fewer patients for more expensive and less effective immunotherapies for the sake of cost containment ("penny-wise, pound foolish.")

This is the reality of private practice today and which is why I (and others) automatically do not jump with joy whenever a new trial is published with a super expensive drug with marginal benefit.
relative bargain- was bad sarcasm- It is not sustainable. CAR T will inevitably come to other tumor types- I already have melanoma pt on trial at NCI- and be combined with immunotherapy. 500,000$ treatments will simply crash our budget and we will be left with a one payer system (and too many radoncs!).
 
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medgator

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looking at our practice and others (as medgator alludes to above) radiation is actually highly cost efficient and clinically effective. However, the gatekeepers of all things financial will be Medical Oncologists, not Radiation Oncologists. Therefore, unless you are in a well-integrated group, Rad Oncs run the risk of seeing fewer patients for more expensive and less effective immunotherapies for the sake of cost containment ("penny-wise, pound foolish.")

This is the reality of private practice today and which is why I (and others) automatically do not jump with joy whenever a new trial is published with a super expensive drug with marginal benefit.
All the more reason to maintain direct referral relationships with friendly/independent surgical and medical specialists when possible.

We're integrated with med onc but I can't remember the last time a H&N or gyn onc referral didn't cross my desk first..... or a case of hemoptysis. I usually end up rotating between med oncs as well surgeons in terms of where they go afterwards for chemo, ports/pegs etc

lymphoma and, especially, mets are where MO ends up driving the referral chain, regardless of one's best efforts and where I believe there will be more med onc scrutiny on xrt.... more 1fx for bone mets, 2 weeks or less for WBRT in situations where srs isn't indicated, less XRT usage in HL and DLBCL etc
 
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Gfunk6

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Some recent germane articles:

New Gene-Therapy Treatments Will Carry Whopping Price Tags
(New York Times) Sept 11, 2017 - Kymriah, approved recently by the F.D.A., with a $475,000 price tag, is first of a coming wave of treatments whose expected prices have alarmed economists, scientists and insurers.

Link: New Gene-Therapy Treatments Will Carry Whopping Price Tags

R and D Costs For Cancer Drugs Are Likely Much Less Than Industry Claims, Study Finds
(NPR/Shots blog) Sept 11, 2017 - Industry says it costs about $2.7 billion to bring a cancer drug to market. But oncologists who ran the numbers put the average closer to $650 million. Drugs are priced way too high, the doctors say.

Link: R&D Costs For Cancer Drugs Are Likely Much Less Than Industry Claims, Study Finds
 
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Palex80

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This may actually draw more patients away from surgery and towards radiochemotherapy for NSCLC.
 

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Statistically speaking it is hard to make sense of a 12% objective response rate (16 vs 28% placebo versus drug) driving such a big difference in progression free survival unless all responders have dramatic long term response, or it decreases incidence of mets with no effect on measurable tumor (also not quite make sense).

Further, while may be good for RT - if you have a drug that works on a certain receptor, and get very positive trial that suggests that and all pre-clinical and other clinical evidence is wrong then two things. Either false positive trial, or as mentioned radiation itself is equivalent to OR induces PDL-1 expression. If latter that is extremely important. Unfortunately even the limited discussion in paper not seem to acknowledge this.
 

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"Study Oversight
The study was designed by representatives of the sponsor (AstraZeneca) and academic advisors. "

What exactly does this mean and should we worry ?
 

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Pacific is an amazing trial. Biggest advance and improvement for lung cancer in over a decade. The design is fantastic and sequence is logical and should support the use of radiation. The main way to reduce costs is not to give 1 year of adjuvant immunotherapy every 2 weeks....
 
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Palex80

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"Study Oversight
The study was designed by representatives of the sponsor (AstraZeneca) and academic advisors. "

What exactly does this mean and should we worry ?
No reason to worry. This is pretty common in most industry-sponsored trials. They call the shots concerning study design, objectives, endpoints. It's basically logical, since a trial like this aims at getting the drug approved for reimbursement for a special indication, thus you need to take all appropriate measures to ensure the FDA does not find a loophole to restrict the indication.
 

medgator

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No reason to worry. This is pretty common in most industry-sponsored trials. They call the shots concerning study design, objectives, endpoints. It's basically logical, since a trial like this aims at getting the drug approved for reimbursement for a special indication, thus you need to take all appropriate measures to ensure the FDA does not find a loophole to restrict the indication.
And use whatever loopholes you can to make the trial look as positive as possible.....
 

Palex80

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And use whatever loopholes you can to make the trial look as positive as possible.....
Perhaps.

But this has been standard practice for quite a long time now.

From the first publication of the Bonner trial results in 2006, which led to cetuximab becoming s.o.c. for H&N-cancer:
"The study was designed by ImClone Systems and the study chairman (J.A.B.) in collaboration with the lead investigators and was managed by ImClone Systems and Merck. ImClone Systems collected and analyzed the data."
 

medgator

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Perhaps.

But this has been standard practice for quite a long time now.

From the first publication of the Bonner trial results in 2006, which led to cetuximab becoming s.o.c. for H&N-cancer:
"The study was designed by ImClone Systems and the study chairman (J.A.B.) in collaboration with the lead investigators and was managed by ImClone Systems and Merck. ImClone Systems collected and analyzed the data."
Perfect example....radiation alone instead of cisplatin+radiation for the control arm in stage IIII/IV H&N cancer.

Erbitux isn't SOC in the US unless a patient would not be able to tolerate high dose q3 week cisplatin

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I've heard this criticism a lot. The cetuximab trial was designed prior to 1999 when cis+RT was not standard of care. The chemo meta-analysis wasn't published until 2000. And a drug that only helps 6-8 out of a 100 people with substantial toxicities in the majority isn't close to a home run/slam dunk.

Perfect example....radiation alone instead of cisplatin+radiation for the control arm in stage IIII/IV H&N cancer.

Erbitux isn't SOC in the US unless a patient would not be able to tolerate high dose q3 week cisplatin

Sent from my SAMSUNG-SM-N910A using Tapatalk
 
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nkmiami

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I am already seeing a lot of stage 4 pts upfront getting keytruda added to platinum/alimeta based on much smaller study and smaller benefit. Many of the major drug studies come from pharma for better or worse.


Major issue with drug pricing is that CMS, by law, is not able to negotiate pricing- they are obligated to pay what the company wants to charge. Apparently Trump was going to change that, but now he is not. Obviously, this is a legalized corruption at its worst. By the same token, there is monopoly pricing by some medical systems.
 
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medgator

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I've heard this criticism a lot. The cetuximab trial was designed prior to 1999 when cis+RT was not standard of care. The chemo meta-analysis wasn't published until 2000. And a drug that only helps 6-8 out of a 100 people with substantial toxicities in the majority isn't close to a home run/slam dunk.
Fair point, although rtog certainly had altered fractionation data by them.

Regarding toxicity, many in the real world would say that erbitux is no walk in the park, and subgroup analysis suggests less of a response in larynx/hypopharynx.
 

medgator

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I am already seeing a lot of stage 4 pts upfront getting keytruda added to platinum/alimeta based on much smaller study and smaller benefit. Many of the major drug studies come from pharma for better or worse.


Major issue with drug pricing is that CMS, by law, is not able to negotiate pricing- they are obligated to pay what the company wants to charge. Apparently Trump was going to change that, but now he is not. Obviously, this is a legalized corruption at its worst. By the same token, there is monopoly pricing by some medical systems.
Ain't that the truth...
 

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Time 0 was at randomization which was after completing CRT so should be lower than in other studies looking at primary definitive treatment. They were also imaging q8w with central imaging review so they probably detected progression events relatively early compared to standard community practice.
 

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Time 0 was at randomization which was after completing CRT so should be lower than in other studies looking at primary definitive treatment. They were also imaging q8w with central imaging review so they probably detected progression events relatively early compared to standard community practice.
Agree. In RTOG 0617, PFS ~11 months, and in PACIFIC control arm PFS ~5 months. However with 0617, randomization was prior to RT (~2 months difference ), and with PACIFIC, randomization started up to 42 days after CRT (up to 1.5 months difference). Additionally, 0617 had q 6 month CT scans following treatment, whereas PACIFC had q 2 months CTs. All things considered, the PFS of the control arm doesn't really seem that far off. I think the OS analysis will help a little more with comparison to historical series.
 
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The PACIFIC Trial is well designed but there a few issues.

1. 25% of patients got induction chemotherapy. For IIIA patients in a curative program induction chemotherapy is a big "no no" in our practice.

2. I'm not incredibly excited for a PFS benefit in curative settings. The answer should lie with Alive vs. Dead and we will need to wait.

3. What the hell do we do with IIIA patients that get adjuvant Darvalumab and inevitably progress? Does it make sense to give another PD-1/L1 therapy after resistance has developed to a PDL-1 drug?

Until there's additional evidence with improved OS, my preference will still to wait till patients progress and can get pembro/Nivolumab (preference to pembro) where there is a demonstrated OS benefit.
 

evilbooyaa

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I wonder if there will truly be a difference in OS on a more mature analysis. Yeah a 3x of PFS seems like a slamdunk, but the decision and subtletly between adjuvant immunotherapy versus early salvage/palliation at time of metastatic recurrence is likely going to be at play here (along with significant cross over in the arms).

Still a benefit and something that will be worth discussion in tumor boards for definitive NSCLC going forward. Ideally, this will push people away from induction chemo + Surgery for N2 disease.

Yes, we all need to worry about the costs of things at some point, but I'm not going to denigrate the study for showing this amount of a PFS benefit.
 

medgator

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Are med oncs giving this drug routinely now? It is in the nccn and FDA breakthrough designation....
 

Palex80

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It's being given in parts of Europe too. I've had 2 patients who got it after CRT for stage III NSCLC.
 

Gfunk6

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This is a huge improvement over RTOG 0617. Median survival on the standard (winning) arm of that trial was 28 months. The median survival of the PACIFIC treatment arm has not yet been reached but from the curves it appears it will be > 36 months.
 

seper

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Toxicity data reported in somewhat unusual way, IMO. I'd expect rare but fatal bleeding (as with Opdivo) and bowel gangrene (Keytruda).
 

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Something will indeed need to be done. 100k/year drugs in oncology are nothing new, but previously were generally used in less common settings. Now with 100k/year immunotherapeutics or novel hormonal agents becoming SOC in many common cancers (lung, prostate, soon to be bladder/kidney, etc), costs are going to spiral like crazy. We need medicare to be able to play the makers of these drugs against each other and cover only the cheapest PD-1/PDL-1, novel hormonal agent, etc. The other drugs can remain available to medicare patients but require an approval process.
 
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