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IMpassion130: Immunotherapy Improves Survival in Patients With Treatment-Naive Metastatic TNBC

1Patients with metastatic triple negative breast cancer (mTNBC) who have PD-L1 positive tumors had improved survival when treated with atezolizumab in combination with nab-paclitaxel, according to late-breaking results from the IMpassion130 trial.

The study, reported at the ESMO 2018 Congress in Munich, is the first to show efficacy of immunotherapy for this type of cancer. First author Peter Schmid said the results “will change the way triple-negative breast cancer is treated.”

mTNBC is the breast cancer subtype with worst prognosis. Once the disease becomes metastatic, the median survival is around 12 to 15 months. Because this type of cancer does not have estrogen receptors or the protein HER2, it is typically treated with chemotherapy, but most patients develop resistance to this treatment within a few months.

Safety and clinical activity of atezolizumab combined with nab-paclitaxel have been demonstrated previously. The IMpassion130 study was a phase 3, double-blind, randomized clinical trial evaluating the treatment combination in patients with mTNBC and ECOG performance status of 0-1 whose tumors had been tested for PD-L1. Patients (n = 902) were randomized 1:1 to intravenous atezolizumab or placebo plus nab-paclitaxel. Stratification factors included treatment with prior taxanes, liver metastases, and tumor PD-L1 status on immune cells (positive: ≥1%). Co-primary endpoints were progression free survival (PFS) and overall survival (OS), evaluated in both the intent-to-treat (ITT) population and the PD-L1 positive subgroup.

At data cutoff, median follow-up was 12.9 months. In the entire study population, the median PFS was 7.2 months with the combination and 5.5 months with chemotherapy alone, with a hazard ratio (HR) of 0.80 (P = .0025). In the PD-L1 positive group, the median PFS was 7.5 months with the combination and 5.0 months with chemotherapy alone (HR = 0.62, P < .0001).

More than half of patients were alive at the time of analysis. In patients with PD-L1 positive tumors, the median OS was 25.0 months with the combination compared with 15.5 months with standard chemotherapy alone (HR 0.62). In all patients, survival was not statistically different between the two groups (21.3 months with the combination vs 17.6 months with chemotherapy alone).

 

Table. IMpassion130a efficacy results

ITT population

PD-L1+ subpopulationb

 

A+nab-P
(n = 451)

P+nab-P
(n = 451)

A+nab-P
(n = 185)

P+nab-P
(n = 184)

 

Co-primary endpointsc

         

Median PFS (95% CI), mo

7.2 (5.6, 7.5)

5.5 (5.3, 5.6)

7.5 (6.7, 9.2)

5.0 (3.8, 5.6)

 

PFS HR (95% CI; P value)

0.80 (0.69, 0.92; P = 0.0025)

0.62 (0.49, 0.78); P < 0.0001

 

Median OS (95% CI), mo

21.3 (17.3, 23.4)

17.6 (15.9, 20.0)

25.0 (22.6, NE)

15.5 (13.1, 19.4)

 

OS HR (95% CI; P value)

0.84 (0.69, 1.02; P = 0.0840)

0.62 (0.45, 0.86); P = 0.0035d

 

Secondary endpointsc

         

ORR-evaluable pts, n

450

449

185

183

 

ORR (95% CI), %

56 (51, 61)

46 (41, 51)

59 (51, 66)

43 (35, 50)

 

Difference in ORR (95% CI), %; P value (Cochran-Mantel-Haenszel)

10 (3, 17); P = 0.0021

16 (6, 27); P = 0.0016

 

DOR-evaluable pts, n

252

206

109

78

 

Median DOR (95% CI), mo

7.4 (6.9, 9.0)

5.6 (5.5, 6.9)

8.5 (7.3, 9.7)

5.5 (3.7, 7.1)

 

OS results based on initial interim OS analysis.

DOR, duration of response; HR, hazard ratio; ITT, intent-to-treat; NE, not estimable; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival.

a NCT02425891.

PD-L1 positivity was defined per the VENTANA SP142 IHC assay as PD-L1 expression on tumour-infiltrating immune cells ≥ 1%.

c PFS, ORR and DOR evaluated per investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1.

Not formally tested due to hierarchical study design.

Schmid said the combination therapy was well tolerated. Most side effects were due to chemotherapy and occurred at a similar rate in both treatment groups, although there was a minor increase in nausea and cough in the combination group. Side effects related to immune therapy were rare, the most common being hypothyroidism which occurred in 17.3% of patients receiving the drug combination and 4.3% receiving chemotherapy alone.

“Immune therapy on top of standard chemotherapy prolonged survival by ten months in patients with tumours expressing PD-L1,” Schmid said. “This combination should become a new treatment option for patients with metastatic triple negative breast cancer.”

Commenting on the results for ESMO, Marleen Kok, medical oncologist, The Netherlands Cancer Institute, Amsterdam, noted that it is still not clear what the best chemotherapy backbone is for anti-PD-L1 treatment.—Kara Rosania

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