Antineoplastics

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

An 82-year-old woman developed weakness, rash, fatigue, anorexia and cough during treatment with pembrolizumab, pemetrexed and catequentinib for advanced lung adenocarcinoma. Additionally, she exhibited treatment failure during treatment with osimertinib, pemetrexed and catequentinib for advanced lung adenocarcinoma [time to reactions onsets and outcomes not stated].

The woman was diagnosed with stage IV poorly differentiated adenocarcinoma of the right lung with adrenal metastasis in December 2017. Subsequently, tumour gene detection revealed L858R gene mutation in exon 21 of epidermal growth factor receptor (EGFR). Her medical history was significant for high blood pressure which was being treated with intermittent unspecified antihypertensive drugs. At the end of December 2017, she started receiving first-line treatment with oral osimertinib [osimertinib mesylate] tablet 80 mg/day. However, in June 2018, a repeat chest CT revealed progressive disease (PD). She continued to receive osimertinib until she visited another hospital on 01 November 2018. The chest and abdominal CT examination revealed pleural and adrenal metastases, and the efficacy was again evaluated as PD.

Osimertinib was discontinued. On 16 November 2018, the woman started receiving second-line treatment with IV drip pemetrexed monotherapy 500mg on day 1 with 3 weeks as 1 cycle. After 2 cycles, the efficacy was evaluated by CT examination as stable disease (SD). However, she complained of intolerability to pemetrexed in the form of grade III weakness. Thus, pemetrexed was stopped after 2 cycles. On 30 January 2019, she started receiving third-line treatment with oral catequentinib [anlotinib hydrochloride] capsules 8 mg administered every other day, day 1−day 14, with 3 weeks as 1 cycle. After 2 cycles, the re-examination showed that the primary lesions in the lungs were slightly larger than before. Her single-drug therapies with osimertinib, pemetrexed and catequentinib had failed. She and her family refused to receive subsequent chemoradiotherapy. On 03 April 2019, she started receiving a fourth-line treatment with IV drip pembrolizumab 100mg once every 3 weeks combined with catequentinib at same dose as before. After 4 cycles of treatment, a repeat CT revealed that the internal solid components of lung lesions were significantly reduced, new cavities were observed inside the lesions, and the efficacy was evaluated as partial response (PR). After 10 cycles, the CT re-examination showed that the lung lesions, pleural and adrenal lesions remained stable and the efficacy was evaluated as persistent PR. Because of the COVID-19 pandemic, pembrolizumab dose was extended to 100mg every 4−6 weeks since January 2020 without any change of dose and cycle of catequentinib. On 03 December 2020, CT scan demonstrated that the pleural and adrenal lesions were similar to before and the efficacy was evaluated as persistent PR. At the time of last telephone follow-up on 12 January 2021, she had received 18 doses of pembrolizumab and 28 cycles of catequentinib, and the progression-free survival (PFS) exceeded 21 months. During the course of pembrolizumab and catequentinib regimen, she developed grade 1−2 treatment-related adverse events in the form of rash, fatigue, anorexia and cough.