This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without ...EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval CI, 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio HR, 0.27 95% CI, 0.11‐0.65; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 95% CI, 0.17‐0.91; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among 40 Japanese patients in the study.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
We evaluated the safety and efficacy of the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) brigatinib in Japanese patients with TKI-naive
ALK
-positive non-small cell ...lung cancer (NSCLC) from the phase 2, open-label, single-arm, multicenter J-ALTA study.
Methods
In the TKI-naive cohort of J-ALTA, the primary end point was independent review committee (IRC)-assessed 12-month progression-free survival (PFS). Secondary end points included objective response rate (ORR), intracranial response, overall survival (OS), and safety.
Results
The data were cut approximately 12 months after last patient enrollment. Thirty-two patients with ALK TKI-naive
ALK
-positive NSCLC were enrolled (median age range, 60.5 29–85 years; median duration of follow-up, 14.2 3.2–19.3 months; median treatment duration, 13.8 0.4–19.3 months). IRC-assessed 12-month PFS was 93.0% (90% confidence interval (CI) 79.2–97.8%); ORR, 96.9% (95% CI 83.8–99.9%), 12-month OS, 96.9% (95% CI 79.8–99.6%), and median OS was not reached. Of five patients with measurable baseline CNS metastases, two had partial intracranial response. The most common treatment-emergent adverse events were increased blood creatine phosphokinase (81%), hypertension (59%), and diarrhea (47%). Grade ≥ 3 adverse events occurred in 91% of patients; pneumonitis was reported in 3 (9%) patients.
Conclusions
In the J-ALTA TKI-naive cohort, brigatinib demonstrated clinically meaningful efficacy consistent with the international phase 3 study. The safety profile in Japanese patients was consistent with previous studies. Brigatinib is an important first-line option for Japanese patients with
ALK
-positive NSCLC.
Clinical registration
NCT03410108
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Necitumumab plus gemcitabine and cisplatin significantly improved overall survival.•Improved progression-free survival and objective response rate were also observed.•Quality of life was not ...negatively impacted by the addition of necitumumab.•Necitumumab plus gemcitabine and cisplatin was well tolerated by patients in Japan.
This open-label, multicenter, phase 1b/2 study assessed necitumumab plus gemcitabine and cisplatin (GC + N) in patients with previously untreated squamous non-small cell lung cancer in Japan.
The phase 1b part determined the gemcitabine dose for the phase 2 part, in which patients were randomized 1:1 to GC + N or gemcitabine and cisplatin (GC) (gemcitabine 1250 mg/m2 on days 1 and 8; cisplatin 75 mg/m2 on day 1 of maximum four 3-week cycles; nectimumab 800 mg on days 1 and 8 of a 3-week cycle continued until progressive disease or unacceptable toxicity). The primary endpoint of the phase 2 part was overall survival.
In the phase 2 part, 181 patients received GC + N (N = 90) or GC (N = 91). Overall survival was significantly improved with GC + N versus GC (median, 14.9 months vs 10.8 months; hazard ratio HR = 0.66, 95% CI: 0.47 – 0.93, p = 0.0161). Improvements were also observed in progression-free survival (median, 4.2 months vs 4.0 months; HR = 0.56; p = 0.0004) and objective response rate (51% vs 21%; p < 0.0001). Survival was also significantly prolonged with GC + N versus GC for patients with epidermal growth factor receptor-positive tumors. Grade ≥3 treatment-emergent adverse events at ≥5% higher incidence with GC + N than GC were neutrophil count decreased (42% vs 35%), febrile neutropenia (12% vs 3%), decreased appetite (11% vs 4%), and dermatitis acneiform (6% vs 0%).
GC + N is well tolerated and has significant and clinically meaningful treatment benefit in the first-line treatment of patients with squamous non-small cell lung cancer in Japan. Clinicaltrials.gov identifier: NCT01763788.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without ...EGFR/ALK alterations and a programmed death‐ligand 1 (PD‐L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression‐free survival by independent central review (data cut‐off date, 10 July 2017) was 0.25 (95% confidence interval CI, 0.10‐0.64; one‐sided, nominal P = .001). The HR for overall survival (data cut‐off date, 15 February 2019) was 0.39 (95% CI, 0.17‐0.91; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or greater. The trial is registered with ClinicalTrials.gov: NCT02142738.
This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among 40 Japanese patients in the study.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
A subset analysis of the CA031 trial showed significant improvement in the overall response rate after administration of carboplatin plus weekly albumin-bound paclitaxel compared to ...carboplatin plus paclitaxel for squamous cell carcinoma of the lung (SQ). We conducted this phase II study to compare carboplatin plus weekly albumin-bound paclitaxel (CnP) to cisplatin plus gemcitabine (CG), a standard regimen for SQ.
Methods
Chemotherapy-naïve patients with SQ were randomly assigned to receive cisplatin (80 mg/m
2
) on day 1 plus gemcitabine (1000 mg/m
2
) on days 1 and 8 every 3 weeks or carboplatin (area under the curve: 6 mg/mL/min) on day 1 plus nab-paclitaxel (75 mg/m
2
) on days 1, 8, and 15 every 3 weeks. The primary endpoint was overall response rate. The secondary endpoints were progression-free survival, overall survival, disease control rate, and toxicity.
Results
Between June 2013 and October 2018, 71 patients were enrolled and assigned to either the CG arm (
n
= 35) or the CnP arm (
n
= 36) of the study. The overall response rate was 43% 95% confidence interval (CI) 27.3–58.5 in the CG arm and 47% (95% CI 31.7–62.7) in the CnP arm. Although drug combination efficacies did not differ, there were differences in toxicity: hematologic toxicities (leukopenia, neutropenia, and thrombocytopenia) were found mostly in the CG arm, whereas anemia and sensory neuropathy were more common in the CnP arm.
Conclusions
CnP had similar response as CG despite being a carboplatin-based regimen and toxicities differed between arms. Regarding ORR, CnP was comparable to CG for SQ.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
BackgroundPD-L1 expression on tumor cells is a marker of PD-1/PD-L1 antibody treatment efficacy for advanced non-small cell lung cancer (NSCLC). PD-L1 antibody (atezolizumab) prolongs overall ...survival (OS) compared with platinum doublet as first-line treatment for NSCLC with high PD-L1 expression. Bevacizumab enhanced cytotoxic agent and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor efficacy in non-squamous (NS)-NSCLC, and PD-1/PD-L1 antibodies in preclinical models.MethodsThis single-arm phase II study investigated clinical benefits of adding bevacizumab 15 mg/kg to atezolizumab 1200 mg fixed dose in a first-line setting for advanced NS-NSCLC patients with PD-L1 expression ≥50% without EGFR/ALK/ROS1 alterations. Primary endpoint was objective response rate (ORR) assessed by central review committee. Secondary endpoints were progression-free survival (PFS), duration of response (DOR), OS, and safety.ResultsOf 39 enrolled patients, 33 (84.6%) had stage IV NSCLC and 36 (92.3%) had smoking history. As of March 31, 2020, no patient had a complete response and 25 patients had a partial response (ORR=64.1%, 95% CI 47.18 to 78.80). Twelve-month PFS and OS rates were 54.9% (35.65 to 70.60) and 70.6% (50.53 to 83.74), respectively. The median DOR in 25 responders was 10.4 months (4.63–not reached). The median treatment cycle was 12 (1 to 27). Nineteen patients discontinued study treatment because of disease progression (N=17) or immune-related adverse events (AEs) (N=2) (sclerosing cholangitis or encephalopathy). There were 23 serious AEs in 12 patients, but no grade 4/5 toxicity.ConclusionsAtezolizumab with bevacizumab is a potential treatment for NS-NSCLC with high PD-L1 expression.Trial registration numberJapicCTI-184038.
Abstract
Background
There is no well‐established late‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of ...platinum rechallenge with paclitaxel‐carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late‐line therapy in a clinical setting.
Methods
Thirty patients with nonsquamous NSCLC who received paclitaxel‐carboplatin with bevacizumab therapy as a late‐line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated.
Results
The median progression‐free survival (PFS) was 6.3 (range, 4.9–6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2–17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (
p
= 0.012). No fatal adverse events were reported.
Conclusions
With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel‐carboplatin and bevacizumab, a late‐line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract only
8500
Background: Adjuvant platinum-based chemotherapy (chemo) provides only a modest 5-year survival benefit in fully resected, high-risk early-stage NSCLC. We report the primary ...disease-free survival (DFS) results from the pre-planned interim analysis of IMpower010, a randomized phase 3 open-label trial of adjuvant atezolizumab (atezo; anti–PD-L1) vs best supportive care (BSC) after adjuvant chemo in patients (pts) with early-stage resected NSCLC. Methods: Eligible pts had completely resected (4-12 weeks prior to enrollment) Stage IB (≥4 cm)-IIIA NSCLC (AJCC/UICC v7) and ECOG PS 0-1. A total of 1280 pts were enrolled, and 1269 pts received up to four 21-day cycles of cisplatin-based chemo (plus pemetrexed, docetaxel, gemcitabine or vinorelbine). Of these pts (n=1269), 1005 were subsequently randomized 1:1 to 16 cycles of atezo 1200 mg Q3W or BSC. The primary endpoint of investigator-assessed DFS and secondary endpoint of overall survival (OS) were tested hierarchically: first DFS in the PD-L1 TC ≥1% (SP263) subgroup with Stage II-IIIA disease, then DFS in all randomized pts with Stage II-IIIA disease, then DFS in the ITT population (Stage IB-IIIA) and finally OS in the ITT population. Efficacy assessments were based on randomized pts. Safety was assessed in the safety-evaluable population, defined as pts who received ≥1 dose of atezo or who had ≥1 post-baseline safety assessment if randomized to the BSC arm. Results: At data cutoff (January 21, 2021), median follow-up was 32.2 months in the ITT population. Baseline characteristics were generally balanced between arms. Atezo showed statistically significant DFS benefit vs BSC in the PD-L1 TC ≥1% Stage II-IIIA and all randomized Stage II-IIIA populations; the significance boundary was not crossed for DFS in the ITT population (Table). OS data were immature and not formally tested. Pts in the atezo arm received a median of 16 (range, 1-16) atezo doses. Any-grade AEs occurred in 92.7% (atezo) and 70.7% (BSC); events were Grade 3/4 in 21.8% and 11.5%, respectively. Grade 5 treatment-related AEs occurred in 0.8% of pts in the atezo arm. AEs leading to atezo discontinuation occurred in 18.2% of atezo-treated pts. Conclusions: IMpower010 met its primary endpoint, showing DFS benefit with adjuvant atezo vs BSC after adjuvant chemo in pts with resected Stage II-IIIA NSCLC, with pronounced benefit in the PD-L1 TC ≥1% subgroup. The safety profile of atezo was consistent with prior experience of atezo monotherapy across indications and lines of therapy. Funding: F. Hoffmann-La Roche Ltd. Clinical trial information: NCT02486718. Table: see text
Background
Diarrhea post-antibiotic use is primarily attributed to
Clostridium difficile
infection (CDI)-induced mucosal lesions, and evidence of CDI in patients undergoing chemotherapy without prior ...antibiotic treatment is also increasing. However, few studies have investigated the relationship between chemotherapy use and diarrhea. This study aimed to determine whether the incidence of CDI increased in patients with lung cancer undergoing chemotherapy even without prior antibiotic treatment.
Methods
We conducted a retrospective study and investigated the presence of
Clostridium difficile
(
C. difficile
) and its toxins in patients who experience diarrhea during chemotherapy. If grade 2 or higher diarrhea was noted, a stool culture was performed to detect anaerobic organisms and
C. difficile
toxins A and B.
Results
A total of 345 consecutive patients (492 in terms of chemotherapy regimens) were enrolled in the study. Grade 2 or higher diarrhea was observed in patients using 36 (7.3%) of these regimens, among which CDI without prior antibiotic exposure was confirmed in patients using 8 regimens (22.2%).
Conclusions
CDI may remain undetected in patients undergoing chemotherapy even in those who had not received antibiotic treatment previously, unless due attention is paid to its possibility. Testing for
C. difficile
toxins is highly recommended to expedite timely treatment for diarrhea in such patients. Further studies are needed to clarify the relationship between chemotherapy drug use and CDI to facilitate prevention.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
This phase II trial was designed to evaluate the efficacy and safety of S‐1 combined with weekly irinotecan as a second‐ or third‐line treatment for patients with advanced or ...recurrent squamous cell lung cancer.
Methods
Patients with a body surface area <1.25, 1.25–1.50, and >1.50 m
2
received oral S‐1 on days 1–14 at 80, 100, and 120 mg/day, respectively, and irinotecan on days 1 and 8 at 70 mg/m
2
every 3 weeks. The primary endpoint was the overall response rate, and the secondary endpoints were progression‐free survival, overall survival, and the incidence and severity of adverse effects.
Results
Between September 2011 and December 2014, 30 patients were enrolled in this study. The overall response rate was 6.7% (95% confidence interval CI: 0.8%–22.1%), and the disease control rate was 73.3%. The median progression‐free survival was 3.0 months (95% CI: 2.5–3.4 months), and the median overall survival was 10.5 months (95% CI: 5.6–13.7 months). Grade 3/4 treatment‐related adverse events were reported in ≥10% of the patients, including leukopenia (21%), neutropenia (21%), anemia (17%), anorexia (10%), and hypokalemia (10%).
Conclusions
Although the treatment‐related adverse events were manageable, the combination of weekly irinotecan and S‐1 did not have the expected effect.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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