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14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Prof Winnie Yeo, 6 days ago
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Christina Lau, 14 Jul 2020

Flat-dose nivolumab, administered as a 30-minute infusion, is well tolerated and active in Asian patients with previously treated advanced non-small-cell lung cancer (NSCLC), according to results of the phase IIIb CheckMate 870 study.

Dr. Michael Tsz-Yeung Kam, 04 Jun 2020

Third-generation EGFR tyrosine kinase inhibitors (TKIs) targeting the EGFRT790M mutation, such as osimertinib, have brought significant improvements to the management of EGFR-positive non-small-cell lung cancer (NSCLC). However, optimization of EGFRT790M mutation testing remains challenging in clinics. At a symposium organized by the Hong Kong Cancer Therapy Society, Dr Michael Tsz-Yeung Kam, Specialist in Clinical Oncology in Hong Kong, discussed real-world challenges in EGFRT790M testing and the current workflow at his centre.

Prolonged survival in a young patient with advanced NSCLC treated with a PD-1 inhibitor

Dr. Michael Tsz Yeung Kam
Clinical Oncology Department
Pamela Youde Nethersole Eastern Hospital
Hong Kong
10 Oct 2019
Presentation and management
A 33-year-old male patient, current smoker with a past history of asthma, presented to the medical department in February 2016 for left-sided chest pain and shortness of breath. Chest X-ray showed a left upper zone shadow. Subsequent CT and PET-CT scans revealed an 8 cm hypermetabolic mass in the left upper lobe with enlarged left paratracheal and supraclavicular lymph nodes. CT-guided biopsy confirmed poorly differentiated, TTF-1–positive non-small-cell lung cancer (NSCLC). Molecular testing was negative for EGFR and ALK mutations. Disease staging was cT4N3, indicating inoperable locally advanced NSCLC. 

Induction chemotherapy with cisplatin plus pemetrexed was initiated, which was complicated by fever after the 1st cycle.  Disease progression was also suspected due to worsening of chest pain after the 2nd cycle.

Induction chemotherapy with cisplatin plus pemetrexed was initiated, which was complicated by fever after the 1st cycle.  Disease progression was also suspected due to worsening of chest pain after the 2nd cycle.

Unfortunately, CT scan in June 2016 after the 2nd cycle revealed disease progression with primary tumour enlargement (size, 11.4 cm) and new intrapulmonary and celiac lymph node metastases. Clinically, the patient also complained of increasing chest pain. His functional status declined rapidly and he became wheelchair-bound. Further molecular testing was not feasible due to inadequate tissue sample. Re-biopsy was attempted and further molecular testing was negative for RET, MET, ROS1 and BRAF mutations. Meanwhile, palliative radiotherapy to the thorax was arranged but did not help with his symptoms.

In August 2016, the patient was commenced on intravenous nivolumab 180 mg every 2 weeks. After two cycles of treatment, the patient had noticeable symptom improvement with reduced chest pain and the ability to walk unaided. Follow-up CT scan in October 2016 showed drastic primary tumour shrinkage (size, 6.5 cm) as well as interval reduction in size of intrapulmonary and celiac lymph node metastases. (Figure 1) Partial response (PR) was confirmed by CT in November 2016.


Prolonged survival

Treatment with nivolumab was well tolerated and the patient did not experience any noticeable side effects. Regular reassessment CT scans showed further primary tumour shrinkage, with the size of tumour remaining static since 2017. As of June 2019, the patient had completed 71 cycles of nivolumab, with treatment well tolerated and no complaints of side effects.

The patient is currently asymptomatic with regular use of analgesics. With regular follow-up, he will continue nivolumab therapy until disease progression.

Discussion
Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis are the new standard of care for patients with squamous or non-squamous advanced non-small-cell lung cancer (NSCLC) without actionable driver mutations who failed first-line platinum-based chemotherapy.1 Nivolumab is a PD-1 inhibitor that has demonstrated favourable tolerability and long-term overall survival (OS) benefit vs docetaxel in the treatment of NSCLC, regardless of PD-L1 expression level (≥1 percent or <1 percent) and histology, in the second-line setting.2-7

In two phase III randomized clinical trials, CheckMate 057 (n=582) and CheckMate 017 (n=272), which included patients with advanced nonsquamous and squamous NSCLC, nivolumab significantly prolonged OS and demonstrated a favourable safety profile compared with docetaxel in the second-line setting.2,3

A pooled analysis of CheckMate 057 and CheckMate 017 showed higher 2-year OS rates with nivolumab vs docetaxel in squamous (23 percent vs 8 percent) and nonsquamous NSCLC (29 percent vs 16 percent).4 Three- and 4-year follow-up data continued to demonstrate higher OS rates with nivolumab (17 percent vs 8 percent at 3 years and 14 percent vs 5 percent at 4 years) in the pooled population, with a median OS of 11.1 months in the nivolumab arm vs 8.1 months in the docetaxel arm.5,6 Notably, the 4-year OS rates were higher with nivolumab vs docetaxel regardless of PD-L1 expression, although the OS benefit was greater in patients with ≥1 percent PD-L1 expression vs those with <1 percent PD-L1 expression (20 percent vs 4 percent and 9 percent vs 4 percent, respectively).6 Nivolumab also demonstrated improved OS vs docetaxel in patients with liver metastases (hazard ratio [HR], 0.68; 95 percent confidence interval [CI], 0.50 to 0.91).5

Similarly, the phase III CheckMate 078 trial in 504 patients (predominantly Chinese) with squamous or nonsquamous NSCLC progressing during/after platinum-based doublet chemotherapy demonstrated significantly improved OS with nivolumab vs docetaxel (median, 12 months vs 9.6 months; HR, 0.68; 97.7 percent CI, 0.52 to 0.90; p=0.0006) after a minimum follow-up of 8.8 months.8

In addition, updated results of the phase I CheckMate 003 study reported a 5-year OS rate of 16 percent for NSCLC patients treated with nivolumab (n=129), and the OS rate was similar between patients with squamous (16 percent) and nonsquamous (15 percent) histology.7

As evidence suggests that most of the responses to nivolumab and docetaxel occurred during the first 6 months of treatment, a landmark OS analysis by response category at 6 months was conducted using the pooled data of CheckMate 003, 063, 017 and 057 studies. Patients with complete response (CR)/PR at 6 months were found to have a substantially higher 4-year OS rate with nivolumab compared with docetaxel recipients with the same response status (58 percent vs 12 percent).6 (Figure 2) The median duration of response was much longer with nivolumab vs docetaxel (24 months vs 6 months), suggesting a greater durability of response benefit with nivolumab.6 Nevertheless, patients with stable disease (SD) at 6 months still had a higher OS rate with nivolumab vs docetaxel (19 percent vs 2 percent) after 4 years of follow-up.6 (Figure 2) Nivolumab-treated patients with disease progression after CR/PR or SD also had subsequent survival benefit vs docetaxel-treated patients with disease progression (OS from time of progression, 6.8 months vs 5.4 months). The corresponding 3-year OS rates were 8 percent and 7 percent, respectively.6


Prolonged survival 3 

Nivolumab is generally well tolerated. The most frequently reported nivolumab-related adverse events (AEs) were fatigue, decreased appetite, nausea and asthenia, most of which were low-grade events.5 Long-term safety data for nivolumab from the CheckMate studies demonstrated a favourable safety profile compared with docetaxel, with no new safety signals identified up to 5 years of follow-up.7 Though uncommon, immune-related AEs, such as skin rash, colitis and pneumonitis, can be severe and life-threatening if not detected early and managed appropriately.9 Patients with NSCLC may have an increased risk of developing pneumonitis when treated with PD-1/PD-L1 inhibitors; hence, they should be monitored closely for any immune-related AEs. 9,10

Our patient was young and fit before NSCLC was first diagnosed, but the disease progressed very rapidly despite treatment with chemotherapy. In view of his poor response to first-line treatment and the absence of actionable driver mutations, immunotherapy was the best second-line option. Nivolumab was the preferred immune checkpoint inhibitor at that time, based on the good safety profile and established OS benefit vs docetaxel. Initiation of nivolumab treatment does not require prior assessment of PD-L1 expression, which offers convenience to the patient without the need of further biopsy. Nivolumab’s outcome data showed a durable survival benefit following an early response to treatment, which provided the patient with confidence to continue treatment until disease progression.

Following rapid disease progression and symptom worsening of after first-line chemotherapy, the patient received the 2-weekly, instead of 4-weekly, regimen of nivolumab. The frequent dosing along with close monitoring of clinical response and immune-related AEs was suitable and beneficial to the patient. Therefore, the same regimen has been maintained throughout the course of treatment.

In summary, this case illustrates the effective use of nivolumab in a young patient with advanced NSCLC who had few choices of potentially beneficial second-line therapies. The patient showed immediate and remarkable response to nivolumab and achieved PR throughout treatment. Nivolumab has been well tolerated with 71 cycles delivered so far. The patient has remained asymptomatic and free of progression and enjoys prolonged survival – almost 3 years after nivolumab initiation, following rapid disease progression on chemotherapy. 

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Most Read Articles
14 Feb 2020
The phase III CASTOR and POLLUX studies previously demonstrated benefit of daratumumab plus bortezomib and dexamethasone (DVd) or lenalidomide and dexamethasone (DRd) vs standard-of-care (SoC) Vd or Rd regimen in relapsed or refractory multiple myeloma (R/R MM). The latest efficacy and safety results after 4 years of follow-up from CASTOR and POLLUX were presented at the American Society of Hematology (ASH) 61st Meeting & Exposition 2019 held in Orlando, Florida, US.  
Prof Winnie Yeo, 6 days ago
Despite the availability of antiemetics, a substantial proportion of patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting (CINV), significantly impacting treatment compliance and quality of life (QoL). At the 24th Annual Scientific Symposium of the Hong Kong Cancer Institute, Professor Winnie Yeo of the Department of Clinical Oncology, Chinese University of Hong Kong, presented results of a local study showing superior efficacy of the fixed-dose netupitant/palonosetron (NEPA) combination regimen vs aprepitant-based regimen in controlling CINV in breast cancer patients receiving highly emetogenic anthracycline-cyclophosphamide (AC) chemotherapy.
Christina Lau, 14 Jul 2020

Flat-dose nivolumab, administered as a 30-minute infusion, is well tolerated and active in Asian patients with previously treated advanced non-small-cell lung cancer (NSCLC), according to results of the phase IIIb CheckMate 870 study.

Dr. Michael Tsz-Yeung Kam, 04 Jun 2020

Third-generation EGFR tyrosine kinase inhibitors (TKIs) targeting the EGFRT790M mutation, such as osimertinib, have brought significant improvements to the management of EGFR-positive non-small-cell lung cancer (NSCLC). However, optimization of EGFRT790M mutation testing remains challenging in clinics. At a symposium organized by the Hong Kong Cancer Therapy Society, Dr Michael Tsz-Yeung Kam, Specialist in Clinical Oncology in Hong Kong, discussed real-world challenges in EGFRT790M testing and the current workflow at his centre.