SEOM-GECP Clinical guidelines for diagnosis, treatment and follow-up of small-cell lung cancer (SCLC) (2022).

Small-cell lung cancer (SCLC) is a highly aggressive malignancy comprising approximately 15% of lung cancers. Only one-third of patients are diagnosed at limited-stage (LS). Surgical resection can be curative in early stages, followed by platinum-etoposide adjuvant therapy, although only a minority of patients with SCLC qualify for surgery. Concurrent chemo-radiotherapy is the standard of care for LS-SCLC that is not surgically resectable, followed by prophylactic cranial irradiation (PCI) for patients without progression. For extensive-stage (ES)-SCLC, a combination of platinum and etoposide has historically been a mainstay of treatment. Recently, the efficacy of programmed death-ligand 1 inhibitors combined with chemotherapy has become the new front-line standard of care for ES-SCLC. Emerging knowledge regarding SCLC biology, including genomic characterization and molecular subtyping, and new treatment approaches will potentially lead to advances in SCLC patient care.

A Delphi consensus panel about clinical management of early-stage EGFR-mutated non-small cell lung cancer (NSCLC) in Spain: a Delphi consensus panel study.

PURPOSE: This Delphi panel study assessed the level of consensus between medical oncologists on the clinical management of patients with early-stage EGFR-mutated non-small cell lung cancer (NSCLC). METHODS: A modified two-round Delphi approach was used. A scientific committee comprised of medical oncologists developed an online questionnaire. Delphi panel experts rated their level of agreement with each questionnaire statement on a 9-point Likert scale. The questionnaire included 36 statements from 3 domains (clinical management of early-stage NSCLC: 15 statements; role of adjuvant therapy in early-stage NSCLC: 9 statements; and role of adjuvant therapy in early-stage NSCLC with sensitizing EGFR mutation: 12 statements). RESULTS: In round 1, consensus was reached for 24/36 statements (66.7%). Nine statements that did not achieve consensus after the first round were evaluated in round 2, and none of them reached consensus. Overall, 84.4% of the panelists agreed that EGFR mutation testing should be done after surgery. Consensus was not achieved on whether the implementation of EGFR mutation testing in resected early-stage NSCLC could limit the use of adjuvant osimertinib. The panelists recognized the rationale for the use of osimertinib in the adjuvant scenario (88%) and 72% agreed that it may change the treatment paradigm in stage IB-IIIA EGFR-mutated NSCLC. Consensus was not reached on the inconvenience of prolonged duration of osimertinib. CONCLUSIONS: This Delphi study provides valuable insights into relevant questions in the management of early-stage EGFR-mutated NSCLC. However, specific issues remain unresolved. The expert consensus emphasizes the role of adjuvant treatment with osimertinib in this scenario.

Efficacy of nintedanib plus docetaxel in patients with refractory advanced epidermal growth factor receptor mutant lung adenocarcinoma.

BACKGROUND: Anti-angiogenic agents are reported to exert clinical activity in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). We evaluated the outcomes of the combination of docetaxel plus nintedanib in refractory NSCLC patients harboring EGFR mutations. METHODS: We retrospectively analyzed 19 patients with advanced EGFR-mutant NSCLC who had progressed to EGFR tyrosine kinase inhibitors (TKI) and platinum-based chemotherapy receiving docetaxel and nintedanib at 14 Spanish institutions from January 2013 to December 2019. Kaplan-Meier and log-rank tests were used to evaluate progression-free survival (PFS) and overall survival (OS). RESULTS: Median age was 58.9 years (range 42.8-81), 73.7% were female. All patients were Caucasian, and 73.7% were never or light smokers. The baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0-1 in 94.7% of patients. All patients had adenocarcinoma. Brain and liver metastases were present in 47.4% and 31.6% of patients, respectively. The most common EGFR mutations were exon 19 deletion (52.6%) and exon 21 L858R mutation (36.8%); 47.4% patients presented the EGFR T790M. 94.8% of the patients had received 2-3 previous treatment lines. Docetaxel was administered at 75 mg/m2/3 weeks to 16 patients, at 60 mg/m2 to 2 patients and at 45 mg/m2 to one patient. Nintedanib was given until disease progression or unacceptable toxicity at 200 mg twice daily except in 2 patients who received 150 mg twice daily and one patient who received 100 mg/12 h. With a median follow-up of 11.4 months (1-38), the median PFS was 6.1 months [95% confidence interval (CI), 4.9-7.3] and the median OS 10.1 months (95% CI 5.9-14.3). The objective response rate (ORR) was 44.4% (23.7-66.8%) and the disease control rate (DCR) 72.2% (49.4-88.5%). Efficacy tended to be greater in patients with the acquired T790M who had received osimertinib, with a median PFS of 6.3 (95% CI 2.1-10.5) versus (vs.) 4.8 (95% CI 3.5-6.1) and a median OS of 12.3 months (95% CI 8.6-16.0) vs. 6.7 months (95% CI 3.9-9.4), although this tendency was not statistically significant (p = 0.468 and p = 0.159, respectively). Sixteen patients (84.2%) had a total of 34 adverse events (AEs), with a median of two (0-6) AEs per patient. The most frequent AEs were asthenia (20.6%) and diarrhea (20.6%). One treatment-related death due to portal thrombosis was reported. CONCLUSIONS: Our data indicate that the combination of docetaxel and nintedanib can be considered to be an effective treatment for EGFR TKI-resistant EGFR-mutant NSCLC.

Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL).

OBJECTIVES: Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. MATERIALS AND METHODS: GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250 mg daily or gefitinib 250 mg daily plus olaparib 200 mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. RESULTS: Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3-13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1-14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00-1.92; p = 0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. CONCLUSIONS: The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination's safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.

Choroidal metastases from lung adenocarcinoma.

A 32-year-old woman presented with an unknown visual deficit. Fundus examination revealed a lesion compatible with a metastatic focus. Diagnostic workup revealed a lung mass and the biopsy was compatible with lung adenocarcinoma. The intraocular lesion was the only metastatic site at the time of diagnosis. She received local choroidal treatment and further systemic therapy. A pneumonectomy was performed. Five months later she progressed systemically and has since then received several lines of chemotherapy. Choroidal metastases are an infrequent site of systemic dissemination and associated with a poor prognosis, with a median survival of around 2 months if it is the first manifestation of a lung neoplasm. Here we review the literature on choroidal metastases, their treatment options and epidemiology.