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Keytruda (Pembrolizumab) + Chemo Boosts Response

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    Posted: Oct 07 2019 at 8:51pm
Pembrolizumab Plus Chemo Boosts Response in Triple-Negative Breast Cancer

Adding the immunotherapy pembrolizumab (Keytruda) to neoadjuvant chemotherapy improved the pathological complete response rate in patients with early triple-negative breast cancer, according to interim results of the KEYNOTE-522 study presented at the European Society for Medical Oncology Congress 2019, held Sept. 27 to Oct. 1 in Barcelona.


Data also indicated improvement in event-free survival, an important outcome in patients with triple-negative disease, which often recurs early on, experts said.

The study included 1,174 patients with triple-negative disease and randomly assigned them 2:1 to pembrolizumab 200 mg three times a week or placebo, both in combination with 4 cycles of paclitaxel plus carboplatin, then 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. After surgery, patients received pembrolizumab or placebo for 9 cycles or until disease recurrence or unacceptable toxicity, according to the results.

Median follow-up was 15.5 months. Pathological complete response was evaluable in 602 patients. The combination of pembrolizumab plus chemotherapy significantly improved pathologic complete response from 51.2% with placebo to 64.8% with the combination (P=.00055).

“We found a 13.6% difference which is a clinically meaningful benefit,” study author Peter Schmid, MD, PhD, of Barts Cancer Institute, Queen Mary University of London, UK, said in a press release.

Patients assigned to the combination also saw a trend toward improved event-free survival (HR=0.63; 95% CI, 0.43-0.93).

“These are preliminary data, but they provide a strong sign that the addition of immune therapy to neoadjuvant chemotherapy prevents breast cancer recurrence,” Schmid said in the release. “If we prevent recurrence, we cure more patients, but we need longer-term data for confirmation.”

Looking at results by PD-L1 status, the immunotherapy combination resulted in a pathologic complete response rate of 68.9% compared with 54.9% for placebo in the PD-L1-positive population, and 45.3% compared with 30.3% in the PD-L1-negative population.

Commenting on the results for ESMO, Prof Fabrice André, Institut Gustave Roussy, Villejuif, France, said, “This is a good situation to test whether the FDA will approve a drug for triple negative breast cancer based on pathological complete response. The combination of the anti-PD-1 monoclonal antibody pembrolizumab plus chemotherapy could become a standard of care if approved.”

https://www.cancernetwork.com/esmo-breast/pembrolizumab-plus-chemo-boosts-response-triple-negative-breast-cancer



Edited by 123Donna - Oct 14 2019 at 6:55pm
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Kellyless Quote  Post ReplyReply Direct Link To This Post Posted: Oct 08 2019 at 12:55am
I'd like to see a trial with the standard ac, then t - the carb & Taxol then A.C. + Keytruda Is brutal, lots of treatment delays doing it with carb, plus going into A.C. After that is just mean. More women make it thru the standard without delay and far less sick. 
IDC, 2.2 cm, Stage IIb,lumpectomy 1/30/09 ACx4,Tx4 36 rads
6/1/16 Local recurrence same breast, same spot 1.8cm Carb.4x every 3 wks, Taxol 12x once wk. Dbl Mast. PCR!! Reconstruction fail, NED!
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 08 2019 at 8:02am
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 14 2019 at 6:54pm

Dr. Dent Discusses Immunotherapy in Early-Stage Breast Cancer


We spoke with Dr. Rebecca Dent, MD, at the European Society for Medical Oncology Congress 2019, held in Barcelona, Spain from September 27, 2019 to October 1, 2019. Dr. Dent shared her the use of immunotherapy in early-stage breast cancer in relation to the KEYNOTE-522 study.

Transcript:

"The bigger question is ‘what should be the chemotherapy backbone?’  We know that certain chemotherapies can actually act like immunomodulators. If you look at specifically platinum-based chemotherapy, what we know is that actually can suppress some of the immunosuppressive elements of breast cancer, specifically looking at suppression of myeloid stem cells and tumor-associated macrophages. We have the biology to explain why it would work earlier and now we actually have a study that actually looked at that.

The KEYNOTE-522 study was looking at early, triple-negative breast cancer in the neoadjuvant setting…a really representative population with almost half the patients being node-positive. It included PD-L1 positive and PD-L1 negative, but about 80% of those patients were PD-L1 positive. The backbone of this particular study was looking at an anthracycline/taxane-platinum which is the most robust control arm you can have with the highest pathological complete response rates reported in literature and this is plus or minus pembrolizumab in the early breast cancer setting. Then the patients proceeded with surgery and then they continued on pembrolizumab (Keytruda) or a placebo.

This is the first read of the results that were presented at this meeting which showed an impressive improvement in pathological complete response rate, regardless of the definition used. The most stringent definition showed an almost 14% improvement. What was actually most interesting though was you saw an even larger benefit in the PDL-1 negative population. In those patients, again, you see greater than 15, almost 20% improvement in pathological complete response in the PD-L1 negative which we’re actually seeing hints of in some of the smaller phase II studies. Independent of PD-L1 status, immune checkpoint inhibitors seem to work."

https://www.cancernetwork.com/esmo-breast/dr-dent-discusses-immunotherapy-early-stage-breast-cancer




Edited by 123Donna - Oct 14 2019 at 6:58pm
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 15 2019 at 8:21am
Neoadjuvant Pembrolizumab Combo Prolongs pCR in Phase III TNBC Study

Neoadjuvant treatment with the combination of pembrolizumab (Keytruda) and chemotherapy extended pathological complete response (pCR) rates by 13.6 percentage points (CI, 5.4-21.8) compared with chemotherapy alone for patients with early triple-negative breast cancer (TNBC), according to findings from the phase III KEYNOTE-522 study presented at the ESMO Congress 2019.

Additionally, following neoadjuvant therapy and surgery, patients in the pembrolizumab arm went on to receive adjuvant pembrolizumab, which was compared with a matched placebo arm. After a median of 15.2 months of follow-up, the event-free survival (EFS) rate with pembrolizumab was 91.3% compared with 85.3% for placebo; however, this benefit was not yet statistically significant (HR, 0.63; 95% CI, 0.43-0.93).

"The addition of pembrolizumab to platinum-containing chemotherapy resulted in a statistically significant and, in my opinion, also clinically meaningful improvement in pathological complete response rates," Peter Schmid, MD, PhD, from the Barts Cancer Institute, Queen Mary University. "Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab showed a favorable trend for EFS compared with chemotherapy alone, at this very early time with only 15 months of follow up."

The KEYNOTE-522 trial randomized patients with TNBC in a 2:1 ratio to receive pembrolizumab at 200 mg every 3 weeks (n = 784) or placebo (n = 390). All patients received 4 cycles of carboplatin plus paclitaxel followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Following surgery, adjuvant pembrolizumab was continued for 9 cycles or until disease recurrence or unacceptable toxicity. EFS and pCR were dual primary endpoints for the study, which defined pCR as ypT0/Tis or ypN0.

Patients with both node-negative and node-positive TNBC were included in the study. Of those enrolled, tumor stage ranged from T1c N1/N2 to T2 to T4 and N0 to N2, per AJCC criteria. All patients had an ECOG performance status of 0 or 1. Patients were evenly stratified between groups based on nodal status, tumor size, and carboplatin schedule (weekly versus every 3 weeks).

The pCR rate was 64.8% with pembrolizumab plus chemotherapy compared with 51.2% for chemotherapy alone, showing a statistically significant improvement with the PD-1 inhibitor (P = .00055). The benefit remained consistent, regardless of pCR definition. Using the ypT0 ypN0 definition, the pCR rate was 59.9% with pembrolizumab and 45.3% with placebo. By the ypT0/Tis definition, the pCR rate was 68.6% and 53.7%, for pembrolizumab and placebo, respectively.

In the PD-L1–positive group (CPS ≥1; n = 498), the pCR rate was 68.9% compared with 54.9%, for pembrolizumab and placebo, respectively. This was equivalent to a 14.2 percentage point increase (CI, 5.3-23.1). In PD-L1–negative patients (n = 97), the pCR rate was 45.3% with pembrolizumab versus 30.3% for placebo, an 18.3 percentage point increase (CI, -3.3 to 36.8).

For the early EFS analysis, 7.4% of events had occurred in the pembrolizumab arm compared with 11.8% in the placebo group. "There's already a difference between the two curves," said Schmid. "We will have subsequent event-free survival analyses coming out soon." The data lock for the current analysis was April 24, 2019.

"Each phase of the study contributed separately to the overall benefit," Schmid noted. "Pathological CR rate is obviously driven by the neoadjuvant part but when we look at recurrence and event-free survival, that's driven, possibly, by the neoadjuvant and adjuvant path. What we can't answer in this study is if you have a similar benefit with just neoadjuvant chemotherapy and pembrolizumab and how much each part of the treatment contributes."

. . .The FDA has granted a breakthrough therapy designation to pembrolizumab plus neoadjuvant chemotherapy, based on earlier findings for the combination in patients with high-risk, early-stage TNBC from the KEYNOTE-173 and the I-SPY 2 trials. Submission of a supplemental new drug application for pembrolizumab in TNBC is highly likely, based on the KEYNOTE-522 data.

"This is a breakthrough because you can increase pCR and by association you can increase survival. This is an important trial from which we will have a lot of data from in the future," said ESMO expert discussant Giuseppe Curigliano, MD, PhD, head of the Division of Early Drug Development at European Institute of Oncology, Italy. "The combination of immunotherapy plus chemotherapy for early triple-negative breast cancer, according to the data presented here, is a new standard of care for early triple-negative breast cancer."


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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