CONFERENCE UPDATE: WCLC 2020
Neoadjuvant singular immunotherapy versus perioperative chemoimmunotherapy for early-stage lung cancer
Dr. Mariano Provencio, Hospital Universitario Puerta de Hierro, Spain, explained that options to improve poor lung cancer survival include adjuvant treatment for stage I and II and neoadjuvant treatment for stage III disease. Where both neoadjuvant and adjuvant treatments provide a clinically significant improvement of 5% in overall survival, neoadjuvant treatment also provides several theoretical advantages such as attacking micrometastasis from the beginning, better compliance, increased resectability, and better response assessment that enables the study of tumor biology and its treatment effects.
Dr. Provencio asserted, “I strongly believe that the question nowadays is no longer whether immunotherapy will play a role in the adjuvant setting, but whether it will be monotherapy or combined with chemotherapy.” For studies of monotherapy treatment, the sample size is usually less than 40 patients with approximately 33% of lung cancer patients in stage IIIA. Where major pathological response (MPR) to neoadjuvant treatment, defined as less than 10% residual tumor after neoadjuvant therapy, is a potential surrogate endpoint for survival, only 14% to 45% of patients have achieved MPR and 5% to 38% of them have achieved complete pathological response (CR).1 Dr. Provencio pointed out, “I think it is important to emphasize that despite being very early stages, there have been progression of the disease in these treatments with monotherapy in different percentages”. As for trials of chemotherapy in combination with immunotherapy, more than 90% of patients were in stage IIIA. MPR or CR was achieved by around 60% of patients with 70% to 90% of patients underwent downstaging.
Despite having 3 times more patients in stage IIIA disease, more than 3 times lung cancer patients in the combination trials achieved CR and MPR than in the monotherapy trials, indicating that combination chemoimmunotherapy is superior to monotherapy. However, a low proportion of patients have achieved CR and the association with survival outcomes has not been validated in NSCLC.2 Thus, a study was designed to investigate the effects of nivolumab plus paclitaxel-carboplatin in treatment-naïve patients with potentially resectable stage IIIA NSCLC.2
The addition of neoadjuvant nivolumab to chemotherapy was welltolerated and was not associated with surgical delays.2 Compared to adjuvant therapy, neoadjuvant therapy was shown to induce a stronger and more prolonged T-cell immune response that might confer long-term protection.1 Finally, all patients who achieved MPR or CR were alive at 24 months, and the progression-free survival among patients with CR was significantly higher when compared to those with MPR or incomplete pathological response.2 Although studies of longer duration would be needed to validate the association between MPR and the survival of NSCLC patients treated with neoadjuvant immunotherapies, this study suggested that MPR could be a surrogate endpoint for survival and may lower the duration and cost of drug trials in resectable NSCLC.2
Lastly, Dr. Provencio pointed out the utility of biomarkers in identifying patients who would most likely benefit from immunotherapy. While programmed death ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are suggested to be predictive biomarkers, the current study found that both of them were not associated with survival.1,3 A meta-analysis of 6 randomized controlled trials found PD-L1 to be a predictor of objective response rate (ORR), but not overall survival or progression-free survival.4 However, significantly higher ORR was observed in the high PD-L1 expression group when compared to those with low PD-L1 expression.4 Nevertheless, the meta-analysis was limited by small sample size in the low PD-L1 expression group and more randomized controlled trials should be analyzed to corroborate the results.4 On the contrary, high TMB patients treated with ipilimumab immunotherapy were found to have better prognosis than the low TMB patients.3 Moreover, a significantly higher mean mutational burden but no significant difference in PD-L1 expression was observed in tumors with MPR than those without.3
Dr. Provencio concluded, “[Neoadjuvant chemoimmunotherapy] provides more responses, more downstaging and greater survival when compared with historical data. This treatment is a window of opportunity after 20 years without progress.”
The use of daratumumab in multiple myeloma: Developing novel immunotherapy strategies to prolong survival
Multiple myeloma (MM) is a type of clonal neoplasm with substantial morbidity and mortality. With the development of better therapies, MM has transformed from untreatable to still incurable but treatable.1
First-line treatment with immunotherapy in metastatic squamous NSCLC
Immunotherapy has dramatically changed the therapeutic scenario in the treatment-naïve advanced NSCLC. While the single agent pembrolizumab has become the standard first-line therapy in patients with ≥50% PD-L1 expression on tumor cells,
Atezolizumab approved for metastatic triple-negative breast cancer
Treatment options were scarce for advanced or metastatic triple-negative breast cancer. Yet, the efficacy of combination therapy with atezolizumab and nab-paclitaxel was illustrated in patients with metastatic triple-negative breast cancer.1
First immunotherapy in PD-L1 positive metastatic triple-negative breast cancer
Atezolizumab plus the chemotherapy nab-paclitaxel has been granted accelerated approval for the first-line treatment of unresectable locally advanced or metastatic, PD-L1-positive triple-negative breast cancer (TNBC) by the United States Food and Drug Administration (FDA).1
Delayed initiation of adjuvant chemotherapy associated with worse outcomes in patients with triple-negative breast cancer
Triple-negative breast cancer (TNBC) accounts for approximately 10-15% of diagnosed breast cancers, one of the most common solid tumors affecting women.1 The European Society for Medical Oncology (ESMO) guidelines
Updates on the latest immunotherapeutic options
The field of immunotherapy has been rapidly evolving and is increasingly utilized in the management of lymphomas.1 Currently, various immunotherapeutic modalities have been pursued including monoclonal antibodies, bispecific T-cell engagers (BiTEs), checkpoint inhibitors and chimeric antigen recepto
Adopting durvalumab consolidation therapy: A breakthough for non-small cell lung cancer treatment
Despite recent advances in oncology, drug resistance and disease relapse have remained a significant unmet need among non-small cell lung cancer (NSCLC). Recently, the development of novel therapeutics including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have made multiple breakthroughs in the treatment of NSCLC. In a virtual meeting and clinical debate, “Durvalumab in EGFRm Stage III NSCLC – To Offer or Not to Offer?”, Dr. Victor Lee summarized the key studies of NSCLC treatments, including the phase 3 PACIFIC trial of an anti-programmed cell death receptor ligand 1 (PD-L1) drug, durvalumab. Dr. Oscar Chan and Dr. Jonathan Nyaw then discussed the applications and other considerations of the durvalumab regimen among stage 3 Epidermal Growth Factor Receptor mutated (EGFRm) NSCLC patients in the clinical setting.
A milestone in biomarker testing and therapies for lung cancer
With advancement in biomarker-driven treatment and targeted therapies for lung cancer, novel strategies are employed to optimize personalized regimens for different subtypes of lung cancer.1 To keep track of the evolving lung cancer management, a symposium regarding biomarker and treatment landscape for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) was held at the World Conference on Lung Cancer 2021.1
Neoadjuvant nivolumab plus chemotherapy shows long-term survival in stage IIIA NSCLC patients: NADIM study
Neoadjuvant chemoimmunotherapy has been shown to be highly effective in non-small-cell lung cancer (NSCLC) at the resectable stage IlIA.1 More than a third of NSCLC patients have stage Ill disease on diagnosis.2 NADIM study is an open-label, multicenter, single-arm phase 2 trial targeting patients with histologically or cytologically documented stage IIIA NSCLC, who were deemed locally to be surgically resectable by a multidisciplinary clinical team and with the Eastern Cooperative Oncology Group (ECG) performance status of O or 1.1 Patients received neoadjuvant treatment with intravenous paclitaxel (200mg/m2) and carboplatin (area under curve 6; 6mg/mL per minute) plus nivolumab (360mg) on day 1 of each 21-day cycle, for 3 cycles before surgical resection; then followed by the adjuvant intravenous nivolumab monotherapy for 1 year (240mg every 2 weeks for 4 months, followed by 480mg every 4 weeks for 8 months).1
Using adjuvant osimertinib to treat resected EGFR mutationpositive NSCLC in early stages: A local case sharing
Accounted for 15.4% of new cancer cases in 2018, lung cancer is one of the most common cancers in Hong Kong, with around 30% of patients having resectable non-small cell lung cancer (NSCLC).1,2 While adjuvant chemotherapy is the current postoperative standard of care, this treatment could only reduce the risk of disease recurrence or death by 16%.2 Recently, the ADAURA trial demonstrated that osimertinib, when utilized as an adjuvant therapy with or without chemotherapy, could prolong the disease-free survival (DFS) of patients with resected stage IB to IIIA epidermal growth factor receptor (EGFR) mutation positive NSCLC.2 In a recent interview with Omnihealth Practice, Dr. Tsang, Wai-Kong Maverick, shared a local patient case with resected stage IB EGFR mutation-positive lung adenocarcinoma who was well-tolerated to the postoperative adjuvant osimertinib without chemotherapy for 10 months.