Lung cancer is one of the deadliest and most common malignancies in the world, representing one of the greatest challenges in cancer treatment. Immunotherapy is rapidly changing standard treatment ...schedule and outcomes for patients with advanced malignancies. However, several ongoing studies are still attempting to elucidate the biomarkers that could predict treatment response as well as the new strategies to improve antitumor immune system response ameliorating immunotherapy efficacy. The complex of bacteria, fungi, and other microorganisms, termed microbiota, that live on the epithelial barriers of the host, are involved in the initiation, progression, and dissemination of cancer. The functional role of microbiota has attracted an accumulating attention recently. Indeed, it has been demonstrated that commensal microorganisms are required for the maturation, education, and function of the immune system regulating the efficacy of immunotherapy in the anticancer response. In this review, we discuss some of the major findings depicting bacteria as crucial gatekeeper for the immune response against tumor and their role as driver of immunotherapy efficacy in lung cancer with a special focus on the distinctive role of gut and lung microbiota in the efficacy of immunotherapy treatment.
•No standard therapy is available for progressing malignant pleural mesothelioma (MPM).•Oligo-progression may occur in selected MPM patients.•In oligo-progressive MPM, high-dose focal radiotherapy ...(FRT) is feasible and safe.•FRT may allow delay of further systemic therapies.
No standard treatment option is available for patients with unresectable malignant pleural mesothelioma (MPM) progressing after upfront chemotherapy. We aimed to explore the role of focal radiotherapy (FRT) as a treatment modality for oligo-progressive MPM.
In this retrospective study, consecutive patients pretreated with ≥1 lines of chemotherapy were included. Oligo-progressive MPM was defined as an unresectable disease with radiological progression at ≤3 sites according to a chest-abdominal contrast-enhanced computed tomography. Patients were treated with either stereotactic body radiotherapy (SBRT, ≥5 Gy per fraction) or hypo-fractionated radiotherapy (hypoRT, <5 Gy per fraction). Time to further systemic therapy (TFST) and local control (LC) after FRT were the primary endpoints. Biologically effective dose (BED) was calculated using three different alpha/beta models (1.5 Gy, 3 Gy and 10 Gy).
From April 2006 to March 2019, 37 patients were treated on 43 pleural lesions; 16/37 (43 %) had undergone upfront multimodality treatment (MMT) including surgery. FRT was given in 22/37 (59.5 %) after one line of chemotherapy. SBRT was delivered for 26/43 lesions (60.5 %), hypoRT for 17/43 (39.5 %). Median TFST was 6 months (95 % CI 4.9–7.1). LC at 6 months and 1 year was 84 % and 76 %, respectively. Median TFST was longer in patients treated after 1 vs >1 line of chemotherapy (9 vs 4 months, p = 0.001) and in patients pretreated with MMT (6 vs 3 months, p = 0.021). Six-month LC was better in patients treated with a BED > 100 using alpha/beta 1.5 and 3. No ≥ G3 acute or late toxicities were reported.
FRT was feasible in selected patients with oligo-progressive MPM, allowing delay of further systemic therapies, with no severe toxicity. FRT was more effective when performed at progression after one line of systemic therapy. Our results suggest a radio-resistant behavior of MPM.
The association of tyrosine kinase inhibitors (TKIs) and local radiotherapy in
-mutated non-small-cell lung cancer patients experiencing disease progression under TKIs could be a valid an option.
We ...included 131 patients experiencing disease progression during first-line TKI. In group A, patients received TKI beyond progression and site(s) of progression were irradiated; in group B, patients remained on TKI alone beyond progression; and group C stopped TKI at first disease progression.
Median overall survival resulted longer in group A versus B and C (p < 0.0001). Group A had a trend toward a longer second progression-free survival (measured from the time of first progression until second progression) versus group B (p = 0.06).
TKI beyond progression in association with local ablative treatment is a valid treatment option in oligoprogressive patients.
With the final aim to explore the first-line treatment options for non-small-cell lung cancer (NSCLC) patients, we performed a systematic review and literature-based meta-analysis of available ...clinical trials exploring immunotherapy in combination versus standard histology-based chemotherapy.
We evaluated interactions according to type of treatment-add-on strategy: immunotherapy in combination versus standard chemotherapy-based regimens. Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted and cumulated.
Seven trials (4278 patients) were included. The addition of immunotherapy to standard chemotherapy-based regimens significantly increased OS (HR 0.74; p = 0.001) and PFS (HR 0.61; p < 0.0001) compared with standard-of-care in NSCLC patients in first-line setting.
Immunotherapy-based regimens constantly improved OS and PFS compared with chemotherapy in first-line treatment of nononcogene-addicted NSCLC.
Background: Epidermal Growth Factor Receptor (EGFR) tyrosine-kinase inhibitors (TKIs) have changed treatment strategies for patients with advanced non-small-cell lung cancer (NSCLC) harbouring ...mutations in EGFR gene. This retrospective analysis assessed efficacy and safety of TKIs in elderly compared to younger patients. Patients and methods: 49 patients with advanced NSCLC and mutations in exon 19 or 21 receiving a first-line therapy with TKIs were included and divided into patients aged <70 years and patients aged ≥ 70 years. Primary endpoints were progression free survival (PFS), response rate (RR) and clinical benefit in terms of quality of life; secondary endpoint was overall survival (OS). Results: Median PFS was significantly longer in elderly in comparison to younger patients (12.6 and 5.6 months, respectively; p= .008). RR was 64% in younger patients and 75% in elderly population. Eighteen out of 20(90%) elderly patients treated with gefitinib experienced symptoms relief and upgrading of performance status. No difference in terms of OS was found (p= .34). Conclusion: TKIs seem more effective in elderly than in younger patients affected by NSCLC with an EGFR gene mutation. We hypothesize that the main difference between the two populations is the number of medications related to concomitant comorbidities that cause an increased plasma level of TKIs.
Before the introduction of tyrosine kinase inhibitors (TKIs) for a particular subgroup of patients, despite platinum-based combination chemotherapy, the majority of patients affected by ...non-small-cell lung cancer (NSCLC) did not live longer than one year. With deeper understanding of tumor molecular biology, treatment of NSCLC has progressively entered the era of treatment customization according to tumor molecular characteristics, as well as histology. All this information allowed the development of personalized molecular targeted therapies. A series of studies have shown that, in some cases, cancer cells can grow and survive as result of the presence of a single driver genomic abnormality. This phenomenon, called oncogene-addiction, more often occurs in adenocarcinoma histology, in non-smokers (except BRAF mutations, also frequent in smoking patients), young, and female patients. Several different driver mutations have been identified and many studies have clearly shown that upfront TKI monotherapy may improve the overall outcome of these patients. The greater efficacy of these drugs is also associated with a better tolerability and safety than chemotherapy, with fewer side effects and an extremely good compliance to treatment. The most frequent oncogene-addicted disease is represented by those tumors carrying a mutation of the epidermal growth factor receptor (EGFR). The development of first, second and third generation TKIs against EGFR mutations have dramatically changed the prognosis of these patients. Currently, osimertinib (which demonstrated to improve efficacy with a better tolerability in comparison with first-generation TKIs) is considered the best treatment option for patients affected by NSCLC harboring a common EGFR mutation. EML4-ALK-driven disease (which gene re-arrangement occurs in 3-7% of NSCLC), has demonstrated to be significantly targeted by specific TKIs, which have improved outcome in comparison with chemotherapy. To date, alectinib is considered the best treatment option for these patients, with other newer agents upcoming. Other additional driver abnormalities, such as ROS1, BRAF, MET, RET and NTRK, have been identified as a target mirroring peculiar vulnerability to specific agents. Oncogene-addicted disease typically has a low early resistance rate, but late acquired resistance always develops and therefore therapy needs to be changed when progression occurs. In this narrative review, the state of art of scientific literature about targeted therapy options in oncogene-addicted disease is summarized and critically discussed. We also aim to analyze future perspectives to maximize benefits for this subgroup of patients.
Background
Identifying the patients who may benefit the most from immune checkpoints inhibitors remains a great challenge for clinicians. Here we investigate on blood serum amyloid A (SAA) as ...biomarker of response to upfront pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC).
Methods
Patients with PD-L1 ≥ 50% receiving upfront pembrolizumab (P cohort) and with PD-L1 0–49% treated with chemotherapy (CT cohort) were evaluated for blood SAA and radiological response at baseline and every 9 weeks. Endpoints were response rate (RR) according to RECIST1.1, progression-free (PFS) and overall survival (OS). The most accurate SAA cut-off to predict response was established with ROC analysis in the P cohort.
Results
In the P Cohort (
n
= 42), the overall RR was 38%. After a median follow-up of 18.5 months (mo), baseline SAA ≤ the ROC-derived cut-off (29.9 mg/L;
n
= 28/42.67%) was significantly associated with higher RR (53.6 versus 7.1%; OR15, 95% CI 1.72–130.7,
p
= 0.009), longer PFS (17.4 versus 2.1 mo;
p
< 0.0001) and OS (not reached versus 7.2mo;
p
< 0.0001) compared with SAA > 29.9 mg/L. In multivariate analysis, low SAA positively affects PFS (
p
= 0.001) and OS (
p
= 0.048) irrespective of ECOG PS, number of metastatic sites and pleural effusion. SAA monitoring (
n
= 40) was also significantly associated with survival endpoints: median PFS 17.4 versus 2.1 mo and median OS not reached versus 7.2 mo when SAA remained low (
n
= 14) and high (
n
= 12), respectively. In the CT Cohort (
n
= 30), RR was not affected by SAA level (
p
> 0.05) while low SAA at baseline (
n
= 17) was associated with better PFS (HR 0.38, 95% CI 0.16–0.90,
p
= 0.006) and OS (HR 0.25, 95% CI 0.09–0.67,
p
< 0.001).
Conclusion
Low SAA predicts good survival outcomes irrespective of treatment for advanced NSCLC patients and higher likelihood of response to upfront pembrolizumab only. The strong prognostic value might be exploited to easily identify patients most likely to benefit from immunotherapy. A further study (FoRECATT-2) is ongoing to confirm results in a larger sample size and to investigate the effect of SAA on immune response in vitro assays.
This single institution Phase II study evaluated drug-eluting beads loaded with irinotecan (DEBIRI) plus capecitabine in pretreated patients with colorectal cancer liver metastases.
Forty patients ...with liver-limited or liver-dominant disease, who have failed at least two previous lines of chemotherapy, underwent either four DEBIRI at 2-week interval or two DEBIRI every 4 weeks for bilobar or single-lobe metastases, respectively. Capecitabine was given at 1000 mg/m
twice-daily on days 1-14 every 3 weeks.
Seven partial responses and 12 stable diseases were observed, achieving a disease control rate of 47.5%. Median progression-free survival and overall survival resulted 4 and 8 months, respectively. Grade 3 adverse events occurred in 6/40 points (15%) of patients.
DEBIRI plus capecitabine is a valid treatment option for heavily pretreated patients with colorectal cancer liver metastases.
Background: We present immunogenicity data 6 months after the first dose of BNT162b2 in correlation with age, gender, BMI, comorbidities and previous SARS-CoV-2 infection. Methods: An immunogenicity ...evaluation was carried out among health care workers (HCW) vaccinated at the Istituti Fisioterapici Ospitalieri (IFO). All HCW were asked to be vaccine by the national vaccine campaign at the beginning of 2021. Serum samples were collected on day 1 just prior to the first dose of the vaccine and on day 21 just prior to the second vaccination dose. Thereafter sera samples were collected 28, 49, 84 and 168 days after the first dose of BNT162b2. Quantitative measurement of IgG antibodies against S1/S2 antigens of SARS-CoV-2 was performed with a commercial chemiluminescent immunoassay. Results: Two hundred seventy-four HWCs were analyzed, 175 women (63.9%) and 99 men (36.1%). The maximum antibody geometric mean concentration (AbGMC) was reached at T2 (299.89 AU/mL; 95% CI: 263.53–339.52) with a significant increase compared to baseline (p < 0.0001). Thereafter, a progressive decrease was observed. At T5, a median decrease of 59.6% in COVID-19 negative, and of 67.8% in COVID-19 positive individuals were identified with respect to the highest antibody response. At T1, age and previous COVID-19 were associated with differences in antibody response, while at T2 and T3 differences in immune response were associated with age, gender and previous COVID-19. At T4 and T5, only COVID-19 positive participants demonstrated a greater antibody response, whereas no other variables seemed to influence antibody levels. Conclusions: Overall our study clearly shows antibody persistence at 6 months, albeit with a certain decline. Thus, the use of this vaccine in addressing the COVID-19 pandemic is supported by our results that in turn open debate about the need for further boosts.
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