番茄社区

At the , over 100 sessions and thousands of abstracts on the latest emerging topics in cancer treatment were presented in all-virtual format. 番茄社区 has brought together three expert leaders in their field: , a breast oncologist at Dana-Farber Cancer Institute; , a thoracic oncology specialist from City of Hope; and , a genitourinary oncologist from the Cleveland Clinic; joined by moderator , of University of California San Francisco's Comprehensive Cancer Center, for a virtual roundtable discussion on the new and potentially practice-changing data from the meeting.

In this first of four exclusive 番茄社区 episodes, the discussion centers on the latest advancements for the treatment of metastatic breast cancer.

Following is a transcript of their remarks:

Hope Rugo, MD: Hello. Welcome to this virtual roundtable, where we will be discussing some of the key data that emerged from this year's ASCO meeting. I'm Hope Rugo, professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco's Comprehensive Cancer Center.

Today I'm joined by three expert leaders in their fields: Dr. Sara Tolaney, a breast oncologist at Dana-Farber Cancer Institute, Dr. Jack West, a thoracic oncology specialist from City of Hope, and Dr. Shilpa Gupta, a genitourinary oncologist from the Cleveland Clinic. Welcome and thanks for joining me.

I'm excited, Sara, that you were able to join us -- Sara Tolaney is a breast medical oncologist, well known to many, who works at Dana-Farber Cancer Institute -- to talk about some of the really exciting data at ASCO 2020 on breast cancer.

One of the studies that we had been waiting for a long time was the results from KEYNOTE-355, a trial in the metastatic setting looking at pembrolizumab with different chemotherapy partners for metastatic triple-negative breast cancer. Tell us a little bit about that study and the results.

Sara M. Tolaney, MD: Sure. Thanks so much for having me and I think that we've all been eagerly awaiting the results from KEYNOTE-355. As you know, we had data from IMpassion130 that had suggested that adding atezolizumab to nab-paclitaxel improved both progression-free survival and overall survival in patients who had PD-L1 positive metastatic triple-negative disease. We were awaiting KEYNOTE-355 because the design is slightly different than the IMpassion130 study.

This trial did allow for patients who had early relapse after adjuvant therapy, so they could have been 6 months out from their adjuvant systemic treatment. There was also choice of chemotherapy for the chemotherapy backbone where physicians could choose either paclitaxel, nab-paclitaxel, or carboplatin and gemcitabine, and then they were randomized to receive that chemotherapy with or without pembrolizumab.

The data demonstrated that adding pembrolizumab to chemotherapy significantly improved progression-free survival in those patients who had PD-L1 positive tumors, with PD-L1 positivity being defined as being with a CPS score greater than or equal to 10 using the 22C3 antibody.

This was about 40% of patients in the KEYNOTE-355 trial that had this significant improvement in PFS. The hazard ratio was about 0.65 with about a 4-month improvement in PFS, so going from around 5.6 months to 9.7 months, so clearly a benefit that was seen. We have not yet seen data regarding overall survival from this trial, so we are still awaiting that, and they also didn't show data looking at objective response rates. We still don't have all the data available, but clearly a very significant improvement in PFS that was seen.

Rugo: I think it's really interesting. There was a change in this course of the study. Originally, the study was powered to look at all comers and then a CPS score of 1 or greater. CPS score uses, as you pointed out, the 22C3 antibody and makes a ratio that includes both tumor as well as the immune cells, so it's a little bit different from the SP142 we're used to looking at.

In a population of patients who have metastatic triple-negative breast cancer, about 80% are positive with a CPS score of 1 or greater, so the trial was actually amended to look at CPS score of 10 or more before they had actually unblinded or looked at any of the data. Actually after the trial had accrued, based on the data from IMpassion130 and then KEYNOTE 119 that also suggested variable benefit from single-agent pembrolizumab based on the scoring. It's really fascinating because it's about the same percentage.

I guess we'll have to wait and look at the survival data from this, but would you feel comfortable now using a checkpoint inhibitor with gem/carbo, for example, if a patient had progressed on a taxane?

Tolaney: Yeah, I think I would. I think it's challenging. Because when you try to look at the subgroup analyses from this trial, if you looked at the forest plot, you could see that those patients who got carboplatin and gemcitabine didn't seem to do as well as those who got taxane.

But yet I think it's important to realize that those patients who got carboplatin and gemcitabine aren't also the early relapsers. Those are the patients predominantly who recurred 6 months after their adjuvant chemotherapy, so they're those patients that were usually within the 12 months of adjuvant treatment.

I think it's hard to know is there differential benefit based on chemotherapy backbone with checkpoint inhibitor therapy because the study wasn't powered to address that question and I don't think we can take away the data from the subgroup suggesting less benefit with platinum to mean that. I think it's just that that was the higher-risk patient population with early relapse, and so I would feel comfortable in an early relapse or to think about chemotherapy with a platinum-based backbone, and checkpoint inhibition. Certainly I'm hoping we will see approval of pembrolizumab to allow for that.

Rugo: It's exciting to see, at least partway through, a positive dataset because it gives us a lot more information, and also data to move to earlier-stage setting, which we're all, of course, looking to anxiously see the data from KEYNOTE-522 from neoadjuvant therapy.

There was one late-breaking abstract that was presented in the plenary session -- we don't get plenary sessions much in breast cancer -- and a long-conducted study, ECOG2108, that looked at taking patients with de novo metastatic disease, and if they had at least stable disease, taking them off their systemic treatment and doing surgery and radiation therapy versus not. It didn't show any difference. Do you take this as a take home message? Should anybody with de novo metastatic breast cancer have surgery? What do we take from that?

Tolaney: No. I think that's a very important study because we've seen two other trials that had had different results, one study suggesting that doing surgery, local therapy in these patients with de novo disease did improve outcomes and whereas another suggesting it did not. This clearly showed that there was no improvement to long-term outcomes by taking these patients to surgery.

That being said, those patients who didn't get local regional treatment did have a higher risk of having local regional events. This was not associated with any difference in quality of life though. I think the take home message to me is that we shouldn't be taking all patients with de novo disease to local therapy after induction chemotherapy.

But for patients who, for example, may be progressing in the breast or having local symptoms, consideration of surgery certainly should be entertained. I think it still leaves us with a lot of questions. I think things have continued to evolve since these studies were initiated, where now there are studies looking at, for example, stereotactic radiation to oligometastatic disease. We also now have much better systemic therapies, for example, for HER2 metastatic disease.

I do wonder if other studies may show differences if, for example, you were to use very optimally-selected patients who got very good systemic HER2-directed treatment and had local therapy for their oligometastatic disease, can we improve long-term outcomes in those select patient populations? I think we just don't know and we need more data.

But for the all-comer population, certainly no role to be taking all our patients to surgery with de novo disease.

Rugo: I think it's a really important point that that's the overall lesson that we've learned now, but that there may be subpopulations who benefit, the long-term survivors, HER2-positive disease, as you pointed out, local regional progression. Then triple-negative disease, where it appeared that stopping therapy actually resulted in a worse outcome, so that would be a different conclusion.

This has been really interesting talking about these two studies. Thank you very much for your comments.

Tolaney: Thanks so much.

Comment