A 49-year-old woman presented with a 6 cm left breast mass and was diagnosed with invasive ductal carcinoma, oestrogen receptor (ER) 0, progesterone receptor (PR) 0, human epidermal growth factor receptor 2 (HER2) 0, and a left axillary node and liver metastases. She had no medical history and her performance status was 0. She took no medications.
She was enrolled on phase III of the IMpassion130 trial in which patients with previously untreated metastatic triple-negative breast cancer were randomised either to atezolizumab (840 mg) 2 weekly plus nab-paclitaxel (100 mg/m2) 3 weeks on/1 week off or to placebo 2 weekly plus nab-paclitaxel (100 mg/m2) 3 weeks on/1 week off.
At cycle 3 she developed a grade 3 rise in aspartate aminotransferase (AST), which was treated with a single dose of methylprednisolone 1 mg/kg followed by 60 mg prednisolone/day. Nab-paclitaxel plus atezolizumab or placebo were withheld for 2 and 4 weeks, respectively. Prednisolone was weaned over 8 weeks and there were no further AST rises.
At cycle 7, amylase was checked as part of a routine blood test and found to be 5.95 μkat/l (grade 3 rise). The patient was asymptomatic. All trial treatment was withheld. An abdominal ultrasound revealed an unremarkable pancreas and no mass. Magnetic resonance cholangiopancreatography (MRCP) showed no evidence of pancreatitis or collection. After 42 days the patient restarted trial treatment following discussion with the medical monitor. The trends in amylase and liver enzymes are shown in Table 22.1 (not all results are consecutive).
At cycle 11 the patient reported grade 1 diarrhoea, which was controlled with loperamide. She continued on trial treatment. The results of investigations at this time are shown in Table 22.2. A planned CT scan 8 weeks later showed mural thickening of the sigmoid colon; therefore, treatment was withheld. At this time, diarrhoea was grades 1–2. A colonoscopy and biopsy revealed colitis and proctitis up to the descending colon. Prednisolone was commenced (40 mg/day).
Nab-paclitaxel and placebo or atezolizumab were restarted after 4 and 6 weeks, respectively, when symptoms were resolved. At this time the patient remained on prednisolone 20 mg/day. Attempts to wean prednisolone further over the next 10 months resulted in recurrent grades 1–2 diarrhoea requiring further steroids. Oral sulfasalazine was trialled but discontinued due to nausea.
A CT scan at cycle 22 showed worsening inflammation of the rectum and sigmoid colon with appearance of ulceration but otherwise stable disease. The prednisolone dose was escalated to 80 mg/day. Nab-paclitaxel was continued; however, atezolizumab or placebo were withheld.
In terms of tumour response, at baseline she had a 5.7cm left breast mass, which was no longer measurable at the cycle 22 scan. At cycle 22 her liver metastases were stable. The left axillary nodes were seen to be increasing in size from cycle 6. A CT-guided biopsy of one of the axillary nodes was performed at cycle 12, which revealed granulomatous lymphadenitis with no malignancy. The lymph nodes ...