Neoadjuvant TCHP + HP for 1 year... anyone???

hi there, I'll be on H&P every 3 weeks for the rest of this year.

Mommyerin, yes, I'm in the US and go to MD Anderson. I finished neo-adjuvant chemo on Monday 5/29 and had CT & MRI on 5/30. Mammo and US showed significant tumor shrinkage and a couple of node tumors can no longer be seen. If the new scans show no progression and I am still considered oligometastic, then I'll have a lumpectomy on 6/27, followed by rads. My first H/P only combo will be on 6/6 and I expect it all to go smoothly, I've had some dry skin but it was the taxane that was hardest but still doable.

Stephanie, I'm glad insurance covered perjeta for you and thanks for reminding us about the trial.

Newbie here...I'm about half-way through neoadjuvant TCHP and they said I'll need Herceptin for a year after that, but no mention of Perjeta continuance. I'll get an ultrasound next week to see if the TCHP is shrinking my tumor.

Mommyerin, just left my MO's office, CT & MRI all good, stable/healing. Lumpectomy is a go for 6/27. I initially thought I would be on Herceptin every 3 weeks for a year but now it looks like Herceptin and Perjeta every 3 weeks forever. It's a pain but at 42 I still have a lot of living to do, so I'll take it.

Mommyerin, like steph said above, there's lots of info, studies, trials showing the benefit of Perjeta, hopefully you'll have no issues.

Hi there! Just thought I'd post since I've been following you all intermittently these past couple of weeks. Wanted to let you know that my Onc went to bat for me with my insurance company and got them to approve Perjeta for a year alongside my Herceptin. What makes this unusual is that I'm adjuvant, Stage 1B, risk 3, HER2+. Since I started chemo on 9/18/17, the lastest study has come out approving Perjeta for adjuvant as well neoadjuvant and metastatic....basically for anybody who is HER2+ which is huge. Since Herceptin and Perjeta only attack cancer cells, this is big news for us. Ask you Onc to pursuse it with your insurance company. It is worth it! Best wishes to Everyone!

Please note that the recent APHINITY trial results, where only a modest improvement in the primary end point of invasive-disease–free survival was observed, was conducted in the setting of ADJUVANT Early Breast Cancer and the results do not necessarily apply to patients differing from the HER2-positive early breast cancer study population in material ways. Importantly, the APHINITY study population did not include any patients with metastatic breast cancer:

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

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

>> "Patients with nonmetastatic, adequately excised, histologically confirmed invasive HER2-positive breast cancer were eligible for participation in the trial."

>> Miller Editorial (2017)(re APHINITY): http://www.nejm.org/doi/full/10.1056/NEJMe1706150

Thus, the findings of APHINITY do NOT apply to those with metastatic breast cancer, in whom a substantial improvement in overall survival was previously demonstrated in another trial (CLEOPATRA):

>> Swain (2015) (CLEOPATRA)(METASTATIC): "Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer"

>> Main Page: http://www.nejm.org/doi/full/10.1056/NEJMoa1413513#t=article

>> Free PDF: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1413513

>> Suppl. Appendix: http://www.nejm.org/doi/suppl/10.1056/NEJMoa1413513/suppl_file/nejmoa1413513_appendix.pdf

>> ASCO Post (2015)(re CLEOPATRA): http://www.ascopost.com/issues/may-25-2015/cleopatra-overall-survival-analysis-significant-benefit-for-pertuzumab-plus-trastuzumabdocetaxel-in-her2-positive-metastatic-breast-cancer/

Any outside publications that influence a person's thinking about treatment plan should be discussed their medical oncologist to ensure proper understanding and applicability to their particular case.

BarredOwl

Interesting bit of news re: the APHINITY results.

https://www.law360.com/articles/931971/roche-faces...

A number of class actions have been launched against Roche for misleading investors in their March 2/17 press release about Perjeta's benefits.

I would argue that the press release wasn't just an overstatement of the benefits, it was patently false. The media release claimed that Perjeta benefits people with HER2 disease, when it only benefits a subset of such patients.

March 2 press release: http://www.roche.com/media/store/releases/med-cor-...

Barred owl, this is the statement that rings false to me:

"The study met its primary endpoint and showed that adjuvant (after surgery) treatment with the combination of Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy (the Perjeta-based regimen) achieved a statistically significant reduction in the risk of recurrence of invasive disease or death (invasive disease-free survival; iDFS) in people with HER2-positive early breast cancer (eBC) compared to Herceptin and chemotherapy alone." (emphasis added)

I am a person with HER2 positive early BC and Perjeta did not reduce my risk of recurrence. Only patients with node positive disease achieved a statistically significant reduction. In my view, it should have said that Perjeta reduces risk for certainpeople with HER2 disease.

Just FYI....since the aphinity trial has concluded, and 6-8 cycles of Herceptin and Pertuzumab were indicated, my insurance company no longer is funding the rest of my Pertuzumab treatment. I had 6 cycles of TCHP and 8 subsequent cycles of HP. Only have 4 more cycles left, and I guess it's going to be just Herceptin. Won't know the results until I'm all done in a couple of months. I think insurance companies are going to use the results of this trial to only fund th 6-8 cycles of chemo so I feel like I'm lucky to have gotten what I have. However, none of our treatments are standard as our cases of cancer are all so different. I'm tired of side effects, especially the tamoxifen now. Just wanting it all to be done so that I can feel like I'm on the other side so I can start healing.

Best wishes to Everyone!!!

Hi Steph:

I would emphasize for other patients that corporate press releases are not typically written by clinicians. The source is an interested party. Press releases are top-line by nature, use layperson's terms, and as such, may lack the precision of peer-reviewed publications.

The Law 360 piece suggests that the investors feel that they were "misled." I have no position on whether the press release may be misleading or not to investors within the meaning of the applicable law.

Re your quote (emphasis added): "The study met its primary endpoint and showed that adjuvant (after surgery) treatment with the combination of Perjeta® (pertuzumab), Herceptin® (trastuzumab) and chemotherapy (the Perjeta-based regimen) achieved a statistically significant reduction in the risk of recurrence of invasive disease or death (invasive disease-free survival; iDFS) in people with HER2-positive early breast cancer (eBC) compared to Herceptin and chemotherapy alone."

I do not think the above statement is "patently false," as you stated initially. By "rings false", perhaps you mean it was "misleading" to you, because you feel that only a certain subset of patients received benefit instead of the group as a whole. However, per the below, the treatment group as a whole DID receive a statistically significant, if modest, benefit.

Re your view that: "Only patients with node positive disease achieved a statistically significant reduction."

This is not correct in my layperson understanding.

Per the NEJM paper (link below), which reports 3-year results relative to "placebo" (which was a trastuzumab-containing regimen), regarding the primary endpoint in the study group as a whole:

>> Overall (absolute difference 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."

A p-value of less than 0.05 is statistically significant. As Dr. Miller noted in the accompanying editorial (link below): "The results with regard to the primary end point, invasive-disease–free survival, were significant. . . The addition of pertuzumab resulted in an absolute 0.9-percentage-point lower rate of recurrence or death at 3 years." (She goes on to discuss this modest benefit in light of the risks.)

Thus, the study did meet its primary endpoint with statistical significance in the study group as a whole, although the size of the absolute difference in IDFS between groups was quite modest (0.9%).

Regarding the relatively modest benefit, above in this thread, in June, you wrote: "If the benefit that Perjeta provides adjuvantly is clinically meaningful . . ." Despite the wording of the March press release, you appreciated that meeting a clinical trial endpoint with statistical significance (e.g., p = 0.045) is a different question from the magnitude of the potential benefit observed (absolute difference 0.9%). And the potential risks must also be weighed.

I agree that the benefit in the node-positive sub-group was statistically significant also:

>> Node-positive sub-group (absolute difference 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)."

The reported statistical findings speak to groups of patients and to potential benefit. There is no way to predict from this whether any individual patient will benefit or not.

Even among patients who (based on the results) may stand to benefit, treatment is not 100% effective, and some portion will still suffer a recurrence. Among these who suffer a recurrence, it is not clear whether they might have benefitted in some way, for example, if their recurrence would have happened earlier than without adjuvant pertuzumab.

Re: "I am a person with HER2 positive early BC and Perjeta did not reduce my risk of recurrence."

From your profile, it looks like you had Stage IIA, node-negative (0/3), hormone receptor-negative disease (ER- PR-), HER2-positive disease.

You made the best decision you could on the available evidence at the time, which had some significant unknowns. I do not think there is any way to know for certain whether you benefitted from adjuvant pertuzumab or not. For example, there might conceivably be some additional known or unknown factors that could affect benefit in particular subsets of node-negative patients, although the results for invasive-disease–free survival were NOT statistically significant in this node-negative group overall.

In addition, as noted in the discussion of the NEJM paper, "A treatment effect was most detectable among patients who were at higher risk for relapse because of lymph-node involvement or hormone-receptor negativity . . ."

In this regard, "In the cohort of patients with hormone- receptor–negative tumors, 71 patients (8.2%) in the pertuzumab group and 91 patients (10.6%) in the placebo group had invasive-disease events (hazard ratio, 0.76; 95% CI, 0.56 to 1.04; P = 0.08); 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)."

The "treatment effect" observed with hormone receptor-negative tumors does not appear to be statistically significant (please confirm it), but it might be considered a trend. You may wish to discuss that particular finding with your MO.

As always, those with pending decisions should discuss any outside information (posts or papers) with their medical oncologist, to ensure accurate understanding and proper application to their case.

BarredOwl

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

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

>> "Patients with nonmetastatic, adequately excised, histologically confirmed invasive HER2-positive breast cancer were eligible for participation in the trial."

>> Miller Editorial (2017)(re APHINITY): http://www.nejm.org/doi/full/10.1056/NEJMe1706150