No abstract

Interleukin-2 (IL-2) is a lymphokine produced by T cells whose main function is to stimulate the growth and cytotoxic response of activated T lymphocytes. It has been used to stimulate the immune system for the treatment of multiples tumors. This article is intended to review the reports published from 1990 to 2004 on the IL-2 treatment of tumors other than melanoma and renal carcinoma. A literature search was made in various databases (MEDLINE, EMBASE and BioAssay), focused on IL-2 clinical efficacy in such tumors. A selection was made over 150 publications reporting on administration of IL-2 in multiple tumors: lung carcinoma (small cell and non-small cell), colorectal, gastric, pancreatic, ovarian and breast cancer, sarcomas, hepatocarcinoma, mesothelioma, and brain, urological, and head and neck tumors. IL-2 was mainly used in metastatic disease, associated with other immunotherapy or chemotherapy schedules. We conclude that adjuvant IL-2 may be of value in early stages combined with standard treatment for colon and pancreas cancers. In other neoplasms, the indication for adjuvant IL-2 has been sporadic and does not allow conclusions to be drawn. Assessment of the efficacy of IL-2 combined with chemotherapy as treatment for advanced stages is complex, due to the lack of a control, and the variety of dosages and schemes. The activity of IL-2 in monotherapy or in association with immunotherapy is clinically relevant in hepatocarcinoma, mesothelioma and in malignant overflows as palliative treatment. Randomized trials would be required in order to be able to draw conclusions about its indication in other tumors.

Interstitial pneumonitis has been described infrequently following administration of docetaxel, used alone or in combination with other chemotherapeutic agents or concurrent irradiation, for non-small-cell lung cancer (NSCLC). This toxicity is of special relevance in NSCLC, as clinical severity and differential diagnosis may be especially challenging. It seems to be due to type I and type IV hypersensitivity reactions to the drug. Clinical and radiographic features are nonspecific and diagnosis is made by exclusion. The rate of grade III-IV docetaxel-induced pneumonitis, ranging from 7 to 47%, depends on several factors, including total dose, chemotherapy schedule and especially concomitant docetaxel treatment with gemcitabine and radiotherapy. Although the usual outcome is cure, it sometimes eventually progresses to pulmonary fibrosis despite steroid treatment. This toxicity must be taken into account when planning treatment strategies for NSCLC in order to reduce its rate and to achieve prompt diagnosis and treatment.

8501 Background: Non-small cell lung cancer (NSCLC) is incurable in most patients with locally advanced stage IIIA disease. Previous results indicate that the use of neoadjuvant chemoimmunotherapy could increase the percentage of cured patients being a promising therapeutic option that has to be tested in randomized clinical trials. Methods: NADIM II (NCT03838159) is an open-label, randomized, two-arm, phase II, multi-center clinical trial. Patients with resectable clinical stage IIIA (per AJCC 7th ed) NSCLC, ECOG PS 0-1, and no known EGFR/ALK alterations were randomized to receive Nivolumab (NIVO) 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) as neoadjuvant treatment followed by surgery, or Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) followed by surgery. Patients with R0 resection confirmed by pathological evaluation initiated adjuvant administration of NIVO within the 3rd to 8th week (+7 days) from surgery and for 6 months. The primary endpoint was pathological complete response (pCR) by blinded independent pathological review (BIPR) in the intent-to-treat population (ITT). pCR was defined as 0% viable tumor cells in resected lung and lymph nodes; patients who did not undergo surgery were classified as non-responders. Major pathological response (MPR; ≤ 10% viable tumor) per BIPR, overall response rate (ORR), toxicity profile, and potential predictive biomarkers are secondary endpoints. Results: Between February 8, 2019, and November 11, 2021, 90 patients were enrolled, of whom 87 patients were valid. Neoadjuvant NIVO + chemo significantly increased the pCR rate compared to chemo in the ITT (36.2% vs 6.8%; Relative Risk (RR) 5.25 [99% CI 1.32-20.87]; P = 0.0071). NIVO + chemo also improved MPR rates vs chemo in the ITT (52 % vs 14 %), as well as ORR (74 % vs 48%). Definitive surgery occurred for 91% of pts treated with NIVO + chemo and 69% with chemo; surgery was cancelled rarely due to AEs (1 pts/experimental arm) and due to disease progression in 1 and 4 pts in the experimental and control arm respectively. Grade 3-4-related AEs were reported in 24 % vs 10% in the NIVO + chemo vs chemo arms, respectively. In the ITT experimental arm, patients with pCR had higher PD-L1 TPS (median 70%, IQR 5-90%) compared to non-responders (median 0%, IQR 0-37.5%, P = 0.0035). AUC to predict pCR was 0.734 (95% CI 0.59-0.88; P = 0.005). The pCR rate rises across increasing categories of PD-L1 TPS ( < 1% 14.3%; 1-49% 41.7%; ≥50% 61.1%; P = 0.008). Conclusions: This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. Thus, this treatment should become the standard of care in these patients. Clinical trial information: NCT03838159.

PurposeThis study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations.Patients and methodsAll newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples.ResultsOf 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8–15.3) months and 17.8 (95% confidence interval: 13.9–21.6) months, respectively, in patients carrying sensitizing mutations.ConclusionThe incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.