Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).

The primary analysis of this trial showed that first-line treatment with osimertinib plus chemotherapy with a platinum-based agent and pemetrexed led to significantly longer progression-free survival than osimertinib monotherapy among patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC). Results from the planned final analysis of overall survival are needed. In this phase 3, international, open-label trial, we randomly assigned in a 1:1 ratio patients with EGFR-mutated (exon 19 deletion or L858R mutation) advanced NSCLC who had not previously received treatment for advanced disease to receive either osimertinib (80 mg once daily) plus chemotherapy with pemetrexed (500 mg per square meter of body-surface area) and a platinum-based agent (cisplatin [75 mg per square meter] or carboplatin [pharmacologically guided dose]) or osimertinib monotherapy (80 mg once daily). The key secondary end point was overall survival. A total of 557 patients were randomly assigned to the osimertinib plus platinum-pemetrexed group (279 patients) or the osimertinib monotherapy group (278 patients). The median overall survival was 47.5 months in the osimertinib plus platinum-pemetrexed group and 37.6 months in the osimertinib monotherapy group (hazard ratio for death, 0.77; 95% confidence interval, 0.61 to 0.96; P = 0.02). Grade 3 or higher adverse events of any cause were reported in 70% of the patients in the osimertinib plus platinum-pemetrexed group and in 34% of the patients in the osimertinib monotherapy group; adverse events leading to the discontinuation of osimertinib were reported in 12% and 7%, respectively. Among patients with EGFR-mutated advanced NSCLC, first-line treatment with osimertinib plus platinum-pemetrexed led to significantly longer overall survival than osimertinib monotherapy and was associated with an increased risk of reversible adverse events of grade 3 or higher. (Funded by AstraZeneca; FLAURA2 ClinicalTrials.gov number, NCT04035486.).

Ewing sarcoma family tumors (ESFT) are heterogeneous, aggressive group of disease with peak incidence in adolescent and young adults. The outcome has been improved dramatically from 10% with surgery and radiotherapy alone to 65%-70% now, in localized disease, with the introduction of chemotherapy. Chemotherapy regimen evolved from single agent to multiagent with effort of many cooperative clinical trials over decades. The usual treatment protocol include introduction of multi-agent chemotherapy in neoadjuvant setting to eradicate systemic disease with timely incorporation of surgery and/or radiotherapy as local treatment modality and further adjuvant chemotherapy to prevent recurrence. Risk adapted chemotherapy in neoadjuvant and adjuvant setting along with radiotherapy has been used in many international collaborative trials and has resulted in improved outcome, more so in patients with localized disease. The role of high dose chemotherapy with stem cell rescue is still debatable. The outcome of patients with metastatic disease is dismal with long term outcome ranges from 20%-40% depending on the sites of metastasis and intensity of treatment. There is a huge unmet need to improve outcome further, more so in metastatic setting. Novel therapy targeting the molecular pathways and pathogenesis of ESFT is very much required. Here we have discussed the current standard of management in patients with ESFT, investigational targeted or novel therapies along with future promises.

The coronavirus disease 2019 (COVID-19) pandemic has imposed a unique challenge to oncology patients and their treatment. There is no study related to the patients’ preference for systemic therapy during this pandemic. We have conducted a prospective study to analyze that aspect. All consecutive patients who visited during the lockdown period from April 1-10, 2020, for systemic chemotherapy were included in the study for a questionnaire-based survey to evaluate the willingness to continue chemotherapy during this pandemic and factors influencing the decisions. A total of 302 patients were included (median age, 56 years; range, 21-77 years). Most common sites of cancer were breast (n = 114), lung (n = 44), ovary (n = 34), and colon (n = 20). Home address was within the city for 125 patients (42%), outside the city for 138 (46%), and outside the state for 37 (12%). Treatment was curative in 150 patients and palliative in 152. Educational status was primary and above for 231 patients and no formal schooling for 71. A total of 203 patients wanted to continue chemotherapy, 40 wanted to defer, and 56 wanted the physician to decide. Knowledge about COVID-19 strongly correlated with intent of treatment (P = .01), disease status (P = .02), knowledge about immunosuppression (P < .001), home location (P = .02), and education status (P = .003). The worry about catching SARS-CoV-2 was high in those with controlled disease (P = .06) and knowledge about immunosuppression (P = .02). Worry about disease progression was more with palliative intent (P < .001). This study shows that oncology patients in our country are more worried about disease progression than the SARS-CoV-2 and wish to continue chemotherapy during this pandemic. The treatment guidelines in the COVID-19 scenario should incorporate patients’ perspectives.

Paediatric sarcomas are a heterogeneous group of disorders constituting bone sarcoma and various soft tissue sarcomas. Almost one-third of these presents with metastasis at baseline and another one-third recur after initial curative treatment. There is a huge unmet need in this cohort in terms of curative options and/or prolongation of survival. In this review, we have discussed the current treatment options, challenges and future strategies of managing relapsed/refractory paediatric sarcomas. Upfront risk-adapted treatment with multidisciplinary management remains the main strategy to prevent future recurrence or relapse of the disease. In the case of limited local and/or systemic relapse or late relapse, initial multimodality management can be administered. In treatment-refractory cases or where cure is not feasible, the treatment options are limited to novel therapeutics, immunotherapeutic approach, targeted therapies, and metronomic therapies. A better understanding of disease biology, mechanism of treatment refractoriness, identifications of driver mutation, the discovery of novel targeted therapies, cellular vaccine and adapted therapies should be explored in relapsed/refractory cases. Close national and international collaboration for translation research is needed to fulfil the unmet need.