Adjuvant TCHP?

Argynis,

Will you stop at six courses or Perjeta in light of the new information revealed by the APHINITY study? In that trial, Perjeta was given for one year. I had five doses of Perjeta and am thinking about asking my MO if I should go back on it. My insurer approved Perjeta indefinitely. Worried that I didn't receive enough of the drug to reap the full benefit.

Thanks

argynis - I did the TCHP neo-adjuavant. I didn't have a pCR, so after surgery I did AC chemo before rads & before resuming Herceptin for the 17 rounds. My MO offered continuing Herceptin AND Perjeta (this was in 2013/4). I had already lost 60 lbs that I couldn't afford to lose, and I was reading about continuing diarrhea with Perjeta so I opted to continue with Herceptin alone. I hope I don't regret it down the road, but we all have to make the best decisions that we can at the time.

i cannot see the part in the trial that says Perjeta was given for 1 year?thanks.

argynis - are you saying you wish there had been an arm of neoadjuvent users that received Perjeta just during the chemo portion, then Herceptin only after chemo was done to compare to the structure of the Aphinity trial? If so, that research had already been done prior to common (standard of care) use of this regimen, and is available on the Perjeta website.

Now I'm confused.

Before Perjeta, the standard of care was TCH plus H (taxotere, carboplatin & herceptin) with continuing herceptin.

Then the standard became neo-adjuvant TCHP with continuing herceptin (TCHP plus H) Part of the clue here is that Pereta was only approved neo-adjuant use at first.

In 2013 I had TCHP with continuing herceptin (TCHP plus H) Perjeta was not initially given without herceptin & was not given during the follow up "year". Because mine was a recurrence, I was offered Perjeta along with herceptin for the follow up "year" even though that was not standard of care at the time. I refused the continuing perjeta because of the side effects.

If I understand what you're saying, you want to see a comparison between the following two treatment choices, which I'm sure has been done or they wouldn't have started adding the P so freely. Is this the question? I'm not a computer guru, but maybe someone else will want to dig out the relevant study.

Comparison of: (TCHP + H) versus (TCHP + H&P)

Thanks BarredOwl.

Argynis: you mention that the APHINITY trial may be structured to give Perjeta for a year to maximize profit. As I understand it, when new medications are developed, the drug trials are run at high dosages to determine whether the drug is effective or not. If the drug is given at a low dose and the trial fails, we don't know whether the failure occurred because the drug itself is ineffective, or, because the patients did not receive enough of the drug. Once the efficacy of the drug is proven, subsequent trials are run to determine whether the dose may be reduced without compromising the effectiveness of the drug. But, perhaps you are right and I am being naive: almost all of the news articles on the recent APHINITY results relate to the Roche share price. Roche has much to gain on the success of this trial.

There is a trial in Finland recruiting patients now that provides only three cycles, every three weeks, of Herceptin and Perjeta (i.e., 9 weeks in total). https://clinicaltrials.gov/ct2/show/NCT02625441 It gives me hope to know that someone out there thinks that three cycles of H & P might be sufficient to conquer the HER2 beast! As you know, I am concerned that I should go back on Perjeta and finish out my year of the drug, along with the Herceptin that I am currently taking. I am reluctant to do it because of the heart trouble I developed while on H and P, and also because I found P to be really difficult to tolerate (deep muscle ache). But, I would go back on Perjeta in a heartbeat if it improves my odds of survival.

Stephanie

As BarredOwl points out it is important to understand the FDA drug approval process. Perjeta was fast-tracked, or given accelerated approval, by the FDA for early stagers based on performance in the Phase II NEOSPHERE trial. Phase II trials measure safety and effectiveness. It was given this type of neoadjuvently administered approval so that data on its effectiveness for early stage Her2+ breast cancer is gathered by measuring pCR at the time of surgery. Part of the motivation for accelerated approval is to allow high risk early stage patients access to proven beneficial medicines before long term survival data is gathered - which takes time. Prescribing Perjeta adjuvently for early stage patients in the clinical setting is technically off-label use, and not routinely done currently. Administering the drug adjuvently in a Phase III trial like APHINITY is to compare this new drug regimen to existing standard of care regimens. APHINITY is an FDA confirmatory trial which is not looking at pCR, but instead at EFS, DFS, and OS when compared to currently existing standard of care.

kae - EFS = event free survival, DFS = disease free survival, OS = overall survival. EFS and DFS are pretty much the same.

just re read the articles and comments above.so if the result of aphinity trial ( results have been favorable so far per articles in the internet but i guess the numbers will be released this june,2017) did show good numbers in adding perjeta adjuvantly with herceptin for a year more after surgery, it will take more time for its approval by the FDA?i finish TCHP in june and i am hoping if results are good maybe it would be approved by then and i can get it along with the H adjuvantly.thanks

anybody know when the result of aphinity trial ( continuing perjeta with herceptin for a year) with numbers will be released?

The APHINITY study results will be presented at the annual ASCO meeting the morning of June 5: http://iplanner.asco.org/am2017/#/

The abstract will be posted on the ASCO website at 7:30 a.m. (ET) on Monday, June 5.

Kae - thanks for the clarification. We'll await further updates.

Further to my post above, the text of the ASCO 2016 abstract re the APHINITY Trial (Von Minckwitz (2017), Abstract No. LBA500) is now publicly available at that link.

In addition, a full-length paper has been published in the New England Journal of Medicine:

>> von Minckwitz (2017), "Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer"

>> Main Page: http://www.nejm.org/doi/full/10.1056/NEJMoa1703643?query=featured_home

>> PDF version: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1703643

>> Supplementary Appendix (data at page 26 et seq.): http://www.nejm.org/doi/suppl/10.1056/NEJMoa1703643/suppl_file/nejmoa1703643_appendix.pdf

There is also an accompanying editorial:

>> Miller Editorial (2017), "Questioning our APHINITY for More"

>> Main Page: http://www.nejm.org/doi/full/10.1056/NEJMe1706150

>> PDF version: http://www.nejm.org/doi/pdf/10.1056/NEJMe1706150

OncLive Feature:

>> http://www.onclive.com/conference-coverage/asco-2017/adjuvant-pertuzumab-may-help-some-early-breast-cancer-patients

Patients with pending treatment decisions should discuss all such articles with their medical oncologist to ensure accurate understanding and applicability in the individual case.

BarredOwl

[Edited to add links to editorial]

Hi Kae_md99:

It looks like you deleted your post while I was writing a reply. By the way, I edited my post above to add a link to an accompanying editorial.

I don't know if the APHINITY trial results are relevant to your situation, because it seems like you received neoadjuvant therapy? In contrast, in APHINITY, it appears that all of the patients all had a surgery-first treatment plan and pertuzumab was administered "adjuvantly" (post-surgery) only.

Perhaps other on-going trials might be more pertinent to your situation? For example, the Discussion of the paper notes: "Ongoing studies are exploring whether after 6 months of neoadjuvant treatment with pertuzumab, patients will require additional treatment after surgery (ClinicalTrials.gov numbers, NCT02131064 and NCT02132949)." Please ask your MO.

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Regarding the APHINITY results (adjuvant pertuzumab-containing regimens), the absolute benefits observed for the primary endpoint of invasive disease-free survival appear to be relatively modest, and were greatest in the node-positive sub-group (1.8% absolute improvement). However, there are some differences between sub-groups. Per the paper, which reports 3-year results relative to "placebo" (which was a trastuzumab-containing regimen):

>> Overall (absolute difference of 0/9%): "The 3-year rate of invasive-disease–free survival was 94.1% in the pertuzumab group and 93.2% in the placebo group, with a hazard ratio for an invasive-disease event of 0.81 (95% confidence interval [CI], 0.66 to 1.00; P = 0.045) in favor of pertuzumab. Distant recurrence occurred as the first invasive-disease event in 112 patients (4.7%) in the pertuzumab group and 139 patients (5.8%) in the placebo group, whereas the numbers of patients with locoregional recurrences were 26 (1.1%) and 34 (1.4%), respectively."

>> Node-positive sub-group (absolute difference of 1.8%): "In the cohort of patients with node-positive disease, the 3-year rate of invasive-disease–free survival was 92.0% in the pertuzumab group, as compared with 90.2% in the placebo group (hazard ratio for an invasive-disease event, 0.77; 95% CI, 0.62 to 0.96; P=0.02)."

>> Node-negative sub-group (absolute difference of 0.9%; P=0.64, not statistically significant): "In the cohort of patients with node-negative disease, the 3-year rate of invasive-disease–free survival was 97.5% in the pertuzumab group and 98.4% in the placebo group (hazard ratio for an invasive-disease event, 1.13; 95% CI, 0.68 to 1.86; P=0.64)."

There were also differences observed according to hormone receptor status:

>>"In the cohort of patients with hormone-receptor–negative tumors . . . the 3-year rate of invasive-disease–free survival was 92.8% in the pertuzumab group and 91.2% in the placebo group (Fig. 2, and Fig. S3 in the Supplementary Appendix)".

>> "In the cohort of patients with hormone-receptor–positive disease,. . . the 3-year rate of invasive-disease-free survival was 94.8% in the pertuzumab group and 94.4% in the placebo group (Fig. 2, and Fig. S3 in the Supplementary Appendix)."

As always, those with pending decisions should discuss with their medical oncologist.

BarredOwl