In the randomized phase 3 trial, patients received neoadjuvant atezolizumab or placebo plus chemotherapy, followed by surgery and adjuvant atezolizumab or observation.
An analysis of patient-reported outcomes showed that, after a brief decline in health-related quality of life (HRQOL) in both the atezolizumab and control arms, the burden of treatment eased and then remained similar throughout follow-up.
“Treatment-related symptoms in both arms were similar, and the addition of atezolizumab to chemotherapy was tolerable, with no additional treatment side-effect bother reported,” said, of the Dana-Farber Cancer Institute in Boston.
She presented these results in an
Primary results of the IMpassion031 trial were reported atand published in .
The trial enrolled patients with treatment-naive early TNBC, and they were randomized to receive chemotherapy plus atezolizumab or placebo. Atezolizumab was given at 840 mg intravenously every 2 weeks.
Chemotherapy consisted of nab-paclitaxel at 125 mg/m2 every week for 12 weeks followed by doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 every 2 weeks for 8 weeks. Patients then underwent surgery, which was followed by either atezolizumab maintenance or observation.
The addition of atezolizumab was associated with a 17% improvement in the rate of pathological complete response (pCR) in the intention-to-treat population.
Among patients positive for PD-L1, atezolizumab was associated with a 20% improvement in pCR rate.
Patients have their say
At SABCS 2020, Dr. Mittendorf presented patient-reported outcomes (PRO) for 161 patients randomized to atezolizumab plus chemotherapy and 167 assigned to placebo plus chemotherapy.
The outcome measures – including role function (the ability to work or pursue common everyday activities), physical function, emotional and social function, and HRQOL – came from scores on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
The exploratory PRO endpoints were mean function and disease- or treatment-related symptoms as well as mean change from baseline in these symptoms.
At baseline, mean physical function scores were high in both arms, at approximately 90%. They dropped to about 65% in each arm by cycle 5 and rebounded to about 80% by cycle 7.
“The change was clinically meaningful, in that the dip was greater than 10 points,” Dr. Mittendorf said. “As patients completed neoadjuvant therapy and were in the adjuvant phase of the study, there was an increase and stabilization with respect to their physical function.”
Similarly, role function declined from 89% in each arm at baseline to a nadir of about 55% in the placebo arm and 50% in the atezolizumab arm. After cycle 5, role function levels began to increase in both arms and remained above 70% from cycle 7 onward.
Role function did not completely recover or stabilize among patients in the atezolizumab arm, “and we attribute this to the fact that these patients continue to receive atezolizumab, which requires that they come to clinic for that therapy, thereby potentially impacting role function,” Dr. Mittendorf said.
She reported that HRQOL declined from a median of nearly 80% at baseline in both arms to a nadir of 62% in the placebo arm and 52% in the atezolizumab arm by cycle 5. HRQOL rebounded starting at cycle 6 and stabilized thereafter, with little daylight between the treatment arms at the most recent follow-up.
The investigators saw worsening of the treatment-related symptoms fatigue, nausea/vomiting, and diarrhea in each arm, with the highest level of symptoms except pain reported at cycle 5. The highest reported pain level was seen at cycle 4.
In each arm, the symptoms declined and stabilized in the adjuvant setting, with mean values at week 16 similar to those reported at baseline for most symptoms. The exception was fatigue, which remained slightly elevated in both arms.
Regarding side-effect bother, a similar proportion of patients in each arm reported increased level of bother by visit during the neoadjuvant phase. However, no additional side-effect bother was reported by patients receiving maintenance atezolizumab, compared with patients in the placebo arm, who were followed with observation alone.
“What we can conclude from the PRO in IMpassion031 is that early breast cancer patients are relatively asymptomatic. They do have a good baseline quality of life and very good functioning. The neoadjuvant therapy certainly has deterioration in quality of life and functioning, but this is transient, and there was no evident burden from the atezolizumab,” said invited discussant, of New York University.
She said it’s reassuring to see the addition of atezolizumab did not adversely affect HRQOL but added that the study “also shows that chemotherapy has a major impact on well-being, as expected.”
Questions and problems that still need to be addressed regarding the use of immunotherapies in early TNBC include whether every patient needs chemotherapy or immunotherapy, a lack of predictive biomarkers, whether increases in pCR rates after neoadjuvant immunotherapy and chemotherapy will translate into improved survival, and the optimal chemotherapy backbone and schedule, she said.
IMpassion031 is sponsored by F. Hoffman-LaRoche. Dr. Mittendorf disclosed relationships with Roche/Genentech, GlaxoSmithKline, Physicians’ Education Resource, AstraZeneca, Exact Sciences, Merck, Peregrine Pharmaceuticals, SELLAS Life Sciences, TapImmune, EMD Serono, Galena Biopharma, Bristol Myers Squibb, and Lilly. Dr. Adams disclosed relationships with Genentech, Bristol Myers Squibb, Merck, Amgen, Celgene, and Novartis.
SOURCE: Mittendorf E at al. SABCS 2020, Abstract GS3-02.