Final Trial results: lapatinib + herceptin improve overall survival meaningfully in

[Lani]

heavily pretreated Stage IVs

hope this helps some of you whose government health systems (or their bean counters) have been hesitant to allow this combination

J Clin Oncol. 2012 Jun 11. [Epub ahead of print]

Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study.
Blackwell KL, Burstein HJ, Storniolo AM, Rugo HS, Sledge G, Aktan G, Ellis C, Florance A, Vukelja S, Bischoff J, Baselga J, O'Shaughnessy J.
Source
Kimberly L. Blackwell, Duke University Medical Center, Durham, NC; Harold J. Burstein, Dana-Farber Cancer Institute; José Baselga, Massachusetts General Hospital, Boston, MA; Anna Maria Storniolo and George Sledge, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN; Hope S. Rugo, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; Gursel Aktan, Catherine Ellis, and Allison Florance, GlaxoSmithKline, Collegeville, PA; Svetislava Vukelja, Texas Oncology, US Oncology, Tyler; Joyce O'Shaughnessy, Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX; and Joachim Bischoff, Otto von Guericke Univeristäte, Madgeburg, Germany.
Abstract
PURPOSEPhase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. PATIENTS AND METHODSPatients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit.ResultsIn this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metastatic sites, and less time from initial diagnosis until random assignment, were associated with improved OS. Incidence of adverse events was consistent with previously reported rates. CONCLUSIONThese data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.
PMID: 22689807

[Lani]

upon reading the article I found the following:

1) Influence of Estrogen Receptor Expression on OS
Of the 128 patients with both HER2-positive and estrogen recep- tor (ER) –positive (locally tested) breast cancer, no differences were observed in OS between the combination arm compared with the monotherapy arm (12 v 11.2 months, respectively; HR, 0.85; 95% CI, 0.57 to 1.26; P �� .404). Conversely, for 163 patients with HER2- positive and ER-negative breast cancer, a significant survival benefit was observed for those receiving combination therapy compared with those receiving lapatinib monotherapy (median 16.5 v 8.9 months, respectively; HR, 0.68; 95% CI, 0.47 to 0.98; P �� .012).


2) Patients with HER2-positive and ER-positive breast cancer did not derive an OS benefit from the com- bination compared with monotherapy. In contrast, patients with HER2-positive and ER-negative breast cancer had a significant OS benefit when administered combination therapy. A similar benefit was noted in subgroups of patients receiving lapatinib plus paclitaxel.22 De- spite the crosstalk between ER and HER2 pathways,23 these data contrib- ute to speculation that absence of ER expression results in HER2-positive breast cancer with enhanced dependence on HER signaling.

Am wondering how many of you who have benefited/not benefited from the
lapatinib+herceptin combo were ER+ as well as her2+, strongly or weakly?

It also turned out to be more effective for those with non-bone mets than for those
with bone mets. Did that seem to be the case for those of you who have tried this
regimen?

I think we should all thank Mauricio Scaltriti who did the original preclinical work under
Jose Baselga for discovering the supersynergism when combining these two agents No they aren't the
cure-all we are all waiting for, but the combination is certainly leading the way to discovering which
combination of targeted treatments will be most effective in which patients.

Every bit of progress helps!

[Mtngrl]

Lani,

Thank you!

I just started this combo. I fall somewhere in the twilight area of the ER and bone issues. My cancer is weakly ER positive, but Arimidex did not prevent progression. My latest PET and CT scans show a lesion in one vertebra that might be a bone met. I also don't have a lot of metastases, unless you count the little lung nodules. One oncologist thinks I've had progression in my lungs. She's someone from whom I sought a second opinion. My own oncologist says it's "not clear" that my lung nodules are cancer.

We shall see. I'm glad the "targeted treatment" idea is getting further refinement.

[hutchibk]

I've had this combo. It's a good one. I now am hoping for the Herceptin/Pertazumab combo. Thanks Lani.

[dchips1]

Almost got 2 years without without any mets, on this combo, especially in the brain. now it is in the thoracic spine. Even though Pertuzamub doesn't cross blood brain barrier I would like to give it a run as well to keep out the pesky rogue cells that always seem to poke into my CNS!!

Lani thanks for all your help and information over all these years. That is valid and is always good to print off articles to take to my onc and we research and plan together the next path in this journey.

Darita

[Bunty]

Thank you Lani yet again! I'll have a chat with my onc as I'm ER-negative. (I can imagine the look on his face when yet again I quote the incredible information I find on this site! At least he's willing to listen, however, not sure what the current Aust Government position is on providing this combo).
Cheers Marie

[michka]

To answer your question Lani:
"Am wondering how many of you who have benefited/not benefited from the
lapatinib+herceptin combo were ER+ as well as her2+, strongly or weakly?"

I continued on Tykerb+Herceptin+Aromasin after being controlled NED several times after first recurrence. I had a worse recurrence 4 months later. The combo did not protect me.I am strongly ER+.
Michka

[Mandamoo]

Marie I'm pretty sure it's not a currently approved combo as I briefly discussed it with my onc prior to starting Tykeeb and Xeloda and she said I would have to self fund herceptin $60000 a year if I wanted to add it to the Xeloda and tykerb. I'm glad there is finally some data to back up what people thought would be helpful. I too am hormone negative with visceral mets - might take this along to my appointment next week.

[Ellie F]

Lani
Thanks again for keeping us so well informed.As you know the UK is one country where lapatinib is not approved by NICE and despite petitions and input from our most senior oncs it still remains the case.
Hopefully this new information will galvanise uk breast cancer charities and other groups to continue to lobby for approval.
I thought this may turn out to be the case with this combo as our hero Dr Slamon has used this for some of his patients for a while.
Ellie

[Lauriesh]

Thanks Lani,

I have been NED on this combo for 16 months. (have a scan coming up, so keeping my fingers crossed that I am still NED) I am er- and had liver mets, so I definitely fit the category as someone this combo is supposed to be more effective for.

This is the boost I needed to stay on it, as I am having so many digestive issues (bloating and gas), that I have been taking extended breaks from the tykerb and was contemplating stopping (which is what my onc wants me to do. In fact, he didn't want me to start it in the first place, and I had to talk him into letting me go on it)

This news will definitely make me keep plugging along on this combo for as long as I can.

Laurie

[MJsHusband]

Is insurance paying for the Tykerb/Herceptin combo since Tykerb was approved only if used with Xeloda? MJ is about to go with a Tykerb-only treatment. If anything is found with the next scans, the plan is to add Herceptin to Tykerb. I just want to make sure it will be payed for by insurance.

Thanks,
GReg

[Lauriesh]

my insurance initially denied it, and I had to write an appeal letter. Thy did decide to cover it.

Hopefully, this study result would be all you need, If you do get denied and have to appeal.



Laurie