Adam M. Brufsky, MD, PhD

Next Steps in Breast Cancer Treatment: Observations From the ASCO20 Virtual Scientific Program

Question

What were the most important takeaways from the plenary session during the ASCO20 Virtual Scientific Program as they relate to breast cancer? What did the results from the phase 3 ECOG-ACRIN study¹ tell oncologists about the potential role of local therapy in de novo, stage IV metastatic disease?

Answer

There are some caveats in this trial and its design, but the most important thing was the finding that when you do early surgery it doesn’t affect survival. Breast cancer is a systemic disease at diagnosis. We knew this in early breast cancer and we know it in metastatic disease.

In this study, if patients had no progression after 4 to 8 months of optimal systemic therapy for metastatic disease, they would be randomized to early local therapy or to continue systemic therapy. There was no difference in overall survival with a [hazard ratio] of 1.09 with 53 months’ follow-up.

Important to me [were] the incidences of locoregional progression, which was 25% for continuous systemic therapy and 10.2% with local therapy. This could be important for patient well-being and control of local complications, and even spread to the pleura.

The question here is that a lot of people with oligometastatic disease have 1 or 2 bone metastases. Do they fit the patients seen in this trial? Was there enough power to see any differences in this population? At [the University of Pittsburg Medical Center Magee-Womens Hospital], this is a big discussion. Selection has to be individualized in people with low burden of metastases or low volume [of] oligometastatic disease.

Question

It has been suggested that the presentation on TRAIN-2 could have practice-changing results in HER2-positive early breast cancer, and that the data appear to show that anthracyclines can safely be omitted from regimens in this patient population.² What is your view on the results of this trial?

Answer

The trial assigned women to FEC (5-fluorouracil, epirubicin, cyclophosphamide) for 3 cycles followed by [paclitaxel, trastuzumab, and carboplatin plus pertuzumab] for 6 cycles or [paclitaxel, trastuzumab, and carboplatin plus pertuzumab] at the same dose and schedule as in the anthracycline group for 9 cycles.

The pathological complete response rate was nearly identical between groups [67% in the anthracycline group and 68% in the non-anthracycline group]. If you look at follow-up, the event-free survival at 3 years was approximately 93% in both arms. Three-year event-free survival is a good measure because in ER-negative, HER2-positive disease, that is when most relapses occur — in the first 3 to 4 years.

It appears we may not need anthracyclines in this disease. There may be tumor heterogeneity in HER2 expression, which would potentially argue for an anthracycline, but in a randomized trial this should be distributed evenly in both arms.

Question

In patients with previously untreated, locally recurrent, inoperable or metastatic triple-negative breast cancer (mTNBC) whose tumors expressed PD-L1, the receipt of pembrolizumab plus chemotherapy was shown to improve progression-free survival compared with chemotherapy alone.³ How do these results, as well as the overall survival (OS) results from KEYNOTE-355, contribute to the understanding of first-line immunotherapy plus chemotherapy in mTNBC?

Answer

KEYNOTE-355 shows essentially similar results as IMpassion130. About 40% of patients (similar to the 40% that are PD-L1–positive in IMpassion130) had [a combined positive score] of greater than or equal to 10. These patients had a median PFS of 9.7 months with chemotherapy and pertuzumab vs 5.6 months with chemotherapy alone (HR, 0.65).

It is important to look at the Forrest plot for subgroups. Patients who relapsed within 12 months appeared to have no benefit [from] pertuzumab.

You also should notice that there were no OS curves in this presentation. I would like to see that whether it is significant or not, and hopefully we will see this by [the San Antonio Breast Cancer Summit] in December [2020].

Question

Do the results seen in PHERGain help oncologists decipher which patients with HER2-positive early breast cancer may be best positioned to achieve a pathologic complete response (pCR) with trastuzumab plus pertuzumab treatment — and also, which patients may avoid chemotherapy altogether?⁴

Answer

The investigators treated women with HER2-positive early-stage breast cancer with either standard neoadjuvant chemotherapy (TCHP) or trastuzumab plus pertuzumab for 2 cycles, or with endocrine therapy if the cancer was ER-positive. If the patients had a response by PET/CT, they continued this therapy. If they did not, they were shifted to TCHP.

The pathologic complete response (pCR) of PET responders who received HP alone with endocrine therapy was 39%. For women with triple-positive disease, the pCR rate was 32.3% overall, 35% as a PET-responder, and 47.7% with TCHP chemotherapy. We will have to wait for the 3-year disease-free survival data to know more.

Question

Please discuss the final results of the BYLieve trial in hormone receptor-positive (HR+), HER2-negative, PIK3CA-mutated advanced breast cancer. In patients whose disease regressed either while receiving treatment or after prior therapy, was there compelling evidence for the subsequent efficacy of alpelisib plus fulvestrant, in your view?

Answer

The idea behind BYLieve was to expand on what to do after progression on a CDK 4/6 inhibitor. Here, they looked at a cohort who had a CDK 4/6 inhibitor and an [aromatase inhibitor] and were given alpelisib plus fulvestrant.

At 1 year, 50% of patients were still alive without disease progression. The median progression-free survival was 7.3 months.

The bottom line for that cohort is that we can use alpelisib and fulvestrant when you have CDK 4/6 failure.