The outstanding performance of existing immunotherapy-TKI than new drugs
The ASCO20 Virtual Scientific Program, which was held online in the aftermath of COVID-19, opened on the 29thand wrapped up its three-day schedule on the 31st of May.
Following the pre-program on the 29th and the opening ceremony on the 30th with a breast and head and neck cancer session, ASCO20 focused on social tasks, from clinical success or failure in various carcinomas to palliative care and anti0-cancer treatment in the COVID-19 era.
NEWSMP organized the major presentations by each session.
◇ Breast Cancer – Tucatinib • Pyrotinibdisclosed Positive Results
In the conference, the joy and sorrow of the latecomers and existing treatments were mixed in the breast cancer field.
While existing treatments have failed repeatedly in new attempts, latecomers seem to be entering the competition by releasing meaningful data in a row.
Seattle Genetics’ Tucatinib (product name Tukysa) derived significant consequences on the phase of HER2CLIMB clinical trials.
The risk of death in brain metastasis HER-2 benign metastasizing breast cancer patients, who has been treated strongly in the past, was reducedto 42% (median overall survival (OS) of 18.1 months vs 12.0 months, HR=0.58) than the placebo group (Trastuzumab + Capecitabine + placebo) with triple therapy of Trastuzumab (original product name Herceptin, Roche), Capecitabine (original product name Xeloda, Roche) and Tucatinib.
Besides, the risk of disease progression or death in the brain was decreased by 68%, the objective response rate (ORR) was 47.3%, higher than 20.0% of the placebo group, and the duration of response (DOR) was 6.8 months, longer than 3.0 months of the placebo group.
Researchers believe that this will be a new standard therapy for HER-2 benign breast cancer patients with or without brain metastasis.
Pyrotinib (product name Hengrui, Jiangsu Hengrui Medicine), which is being developed in China, has also released successful interim analysis results on PHOBEE phase III clinical trials.
In comparison to the Tykerb (lapatinib, GSK), the progression-free survival has improved in brain metastasis HER-2 benign breast cancer patients (12.5 months vs 6.8 months, HR=0.39).
In particular, in trastuzumab-resistant patients, progression-free survival was improved (12.5 months vs 6.0 months, HR=0.60), and the ORR was 67.2%, which was 51.5% higher than the Tykerb.The median DOR recorded 11.1 months, 7.0 months longer than the Tykerb.
Novartis confirmed the potential of the PI3K inhibitor Piqray (Alpelisib) and the CDK4/6 inhibitor Kisqali (Ribociclib).
Piqray issued substantial data for a 6-month progression-free survival rate of 50.4% on phase IIBYLieve study conducted in PIK3CA mutant hormone receptor (HR) positive HER-2 negative breast cancer patients who had previously been treated with CDK inhibitors.
Kisqali relatively produced somewhat ambiguousstudy.Although the FELINE study showed a significant difference in cell cycle arrest and tumor cell activity (Ki-67) between Letrozole + Kisqali combination therapy and Letrozole + placebo as neoadjuvant therapy for hormone receptor-positive breast cancer patients, the difference with the placebo group has disappeared at the time of surgery.
Further analysis is needed since Ki-67 tends to amplify faster from the first cycle to surgery in Kisqali groups.
Abbvie’s PARP inhibitor, Veliparib, also presented ambiguous results in SWOG S1416 phase II, which compared Cisplatin + Veliparib combination therapy to Cisplatin + placebo groups with metastatic triple-negative breast cancer patients who have been treated more than once in the past, or BRCA1/2 related metastatic breast cancer patients.
Although the progression-free survival in both the BRCA positive group and the BRCA-like phenotype group was improved, Veliparib has not achieved statistical significance in the BRCA positive group and have now shown any improvement in the PFS in the non-BRCA group.
Nevertheless, the BRCA-like phenotype groups improved the progression-free survival (HR=0.58, p=0.023), and the overall survival (HR=0.55, p=0.14) and the objective response rate (45% vs 35%, p=0.38) showed an improvement over the placebo group.
The researchers say that further analysis is required for this trend.
MSD’s PD-1 immunotherapy drug Keytruda (Pembrolizumab) has improved the PFS in KEYNOTE-355 clinical trials at CPS 10 or higher (anticancer + Keytruda 9.7 months vs anticancer + placebo 5.6 months, HR=0.65, p=0.012) for patients with unresectable local recurrence metastatic triple-negative breast cancer, but could not find any significance at CPS over 1.
In addition, on SYSUCC-011 phase III, which evaluated continuous low dose capecitabine therapy in triple-negative breast cancer patients in China, found out meaningful changes (83% vs 73% HR=0.56) in the 5-year disease-free survival rate, but not on overall survival.
The NSABP B-43 phase III study, which added trastuzumab to radiation treatment after lumpectomy of ductal carcinoma in situ HER-2 positive patients, the TRAIN-2 phase III, which added anthracycline to 2-3 stage breast cancer patients who had double HER-2 targeted cancer therapy as neoadjuvant chemotherapy, and KAITLIN phase III study, which compared Herceptin + Perjeta + Tak-Sen triple therapy with Kadcyla + Perjeta dual therapy after anthracycline adjuvant treatment in HER-2 positive high-risk early breast cancer patients, did not reach meaningful improvement compared to previous treatments.
In patients with endocrine sensitive visceral metastasis breast cancer, the combination therapy of Ibrance (Palbociclib) and Faslodex (Fulvestrant) had no better aspects in progression-free survival compared to Ibrance + Letrozole, and there was no difference in four-year overall survival.
There was no significant improvement inphase III of the E2018 when topical treatment was added to the systemic therapy of novo 4 metastasis and primary breast cancer patients.
◇ Colorectal cancer – Encorafenib, OS Improvement through Cetuximab Combination Therapy
In the colorectal cancer field, Encorafenib (Braftovi, Pfizer) has improved overall survival and progression-free survival in patients with BRAF V600# mutant metastatic colorectal cancer with previous treatment experiences.
Encorafenib made a worthwhile improvement than anti-cancer chemotherapy in triple therapy, which includes RAS inhibitor Cetuximab (product name Erbitux, Merck) and MEK inhibitor Binimetinib (product name Mektovi, Pfizer) as well as dual therapy which excludes Binimetinib.
The control group was treated by irinotecan + cetuximab or FOLFIRI + cetuximab, and the median overall survival was 9.3 months in the triple therapy group, reducing the risk of death by 40% (HR= 0.60) compared to 5.9 months of the control group as a result of the analysis.
Moreover, the dual therapy also had a median overall survival of 9.3 months, with a 39% lower risk of death than the control group (HR=0.61).
The objective response rate was also 26.8% for triple therapy and 19.5% for dual treatment, resulting in outstanding data than the 1.8% of the control group.
An antibody-drug conjugate (DS8201/A-J203), which is developing by Daiichi Sankyo and AstraZeneca, provided meaningful data in patients with high HER-2 gene mutation rates.
Inphase II of DESTINY-CRC01 for patients with HER-2 positive and RAS wild-type metastatic colorectal cancer, the objective response rate of Cohort A consisting of patients with HER-2 IHC 3+ or IHC 2+/ISH+ was 45.3%, patients previously exposed to targeted therapies was 43.8%, the disease control rate (DCR) was 83.0%, and the median progression-free survival was 6.9 months.
However, there was no reaction from IHC2+/ISH- in cohort B or IHC 1+ in cohort C. The research team evaluated that the activity was confirmed in patients with HER-2 metastatic colorectal cancer that recurred in standard treatment.
Also, the CALGB/SWOG 80702 study, which attempted to improve the disease-free survival (DFS) and overall survival of colorectal cancer patients with Celecoxib (original product name Celebrex, Pfizer), and the ID 3RAphase III trials, which compared the stage 3 colorectal cancer patients who took oxaliplatin + fluoropyrimidine surgery with three-month of adjuvant therapy and six-month therapy, did not find a significant difference.
◇ Gastrointestinal cancer – Herceptin + Perjeta Have Clear Gains and Losses
In the gastrointestinal carcinoma fields, PETRARCA phase II clearly showed the gains and losses of esophageal cancer patients.
After adding Perjeta and Herceptin to FLOT (5-FU, Leucovorin, Oxaliplatin, Docetaxel), the better results showed in pathological complete response rate (pCR, 12% vs 35%), lymph node-negative rate (39% vs 68%), the disease-free survival rate at 22 months (54% vs 70%), and overall survival rate at 22 months (77% vs 84%).
However, the Perjeta + Herceptin addition group had to endure diarrhea (5% vs 41%) and leukocytosis (13% vs 23%).
In the KEYNOTE-061 study, which examined the possibility of Keytruda in the secondary treatment of patients with advanced gastric cancer and adenocarcinoma of the esophageal junction, regardless of the PD-L1 rate (combined positive score), the overall survival, objective response rate, and duration of reaction were improved compared to Paclitaxel.
This study was conducted on patients with PD-L1 positive advanced gastric cancer and adenocarcinoma of the esophageal junction, who had previous treatment experiences.Thethe median of overall survival was 9.1 months at CPS 1 or higher (controlled group 8.3 months, HR=0.81), 10.4 months at CPS 5 or higher (controlled group 8.3 months, HR=0.72), and ten months at CPS 10 or higher (controlled group 8.0 months, HR=0.69).
The objective response rate also showed a similar tendency with 16.3% (controlled group 13.6%) at CPS 1 or higher, 20.0% (controlled group 14.3%) at CPS 5 or higher, and 24.5% (controlled group 9.1%) at CPS 10 or higher. However, the median value of the progression-free survival was shorter for all three groups than the control groups.
Lilly also processed a phase II clinical trial of RAMSES/FLOT7, which added Alimta (Ramucirumab) to the FLOT with resectable adenocarcinoma of the esophageal junction patients.
The result of adding Alimta to the FLOT before and after surgery, the response rate was similar (27% vs 30%). Still, the complete resection rate (R0-resection) (97% vs 83%), surgical morbidity (44% vs 37%), and mortality (5.9% vs 2.5%) were higher in Alimta added group.
In this regard, the researchers explained the Alimta added group had improved the complete resection rate by allowing more patients to operate.
Meanwhile, on phase III of NRG Oncology/RTOG 1010 clinical trials, Herceptin was added to the triple combination therapy of paclitaxel, carboplatin, and radiation to overexpressionesophageal adenocarcinoma patients, but could not bring out an improvement in DFS and OS.
◇ Liver cancer – China Exceeds Sorafenib, Giotrif also Became HCC Treatment
In the liver cancer field, China, which possesses about 50% of the world’s liver cancer patients, made a remarkable achievement.
Zelgen-developed Donafenib (CM-4308) has revealed through ZGDH3 clinical trials that Donafenib has surpassed Bayer’s Nexavar (Sorafenib), which has been the first-line therapy for hepatocellular carcinoma for more than ten years, and Lenvima (Lenvatinib, Eisai), another first-line treatment, improved the DFS with transarterial chemoembolization (TACE).
Furthermore, Chinese researchers have also succeeded in clinical trials of liver cancer with Giotrif (afatinib, Boehringer Ingelheim), which is known to EGFR mutant non-small cell lung cancer treatment.
As a result of administering afatinib in patients with advanced hepatocellularcarcinoma with advanced disease after receiving first-line treatment with Nexavar or Oxaliplatin based chemotherapy, the OS (8.7 months vs 6.8 months, HR=0.789 p=0.0476), PFS (4.5 months vs 1.9 months, HR=0.471 p<0.0001) were improved, as well as ORR (10.7% vs 1.5%).
In the meantime, AstraZeneca identified the possibility of combination therapy of the PD-L1 inhibitor Imfinzi and CTLA-4 inhibitor Tremelimumabin patients with advanced liver cancer who cannot take Nexavar as a treatment.
It was analyzed that the combination therapy of Imfinzi and Durvalumab had more advantages in OS, PFS, or duration of a reaction than each monotherapy.
◇ Renal Cell Carcinoma • Urothelial Cell Carcinoma – Present the Possibility of Various Treatments
In the renal cell carcinoma field, where cancer immunotherapies are on the rise, research results that promise the future have been the main focus.
MSD and Eisai with combination therapy of Keytruda and Lenvima, and BMS and Ono with Opdivo (Nivolumab) and Yeryoy (Ipilimumab) launched the possibility of second-line treatment after the first-line immune checkpoint inhibitor.
Inphase II of Study 111/KEYNOTE-146 for patients with metastatic clear renal cell carcinoma, combined therapy of Keytruda and Lenvima had an ORR of 51% at 12-week follow-up, disease control rate of 91%, median duration of reaction 9.9 months, and the median time to median was 1.6 months.
Also,phase II of the FRACTION-RCC, which was conducted on patients with advancedrenal cell carcinoma, had an ORR of 15.2% at the time of 8.9 months of median follow-up.It was evaluated that 7 out of 46 patients who participated in the study had partial reactions, which could be expected to have partial responses in certain patients.
In advance, AstraZeneca’s c-MET inhibitor Savolitinib revealed the interim analysis data of SAVOIR phase III, which compared MET-induced metastatic papillary renal cell carcinoma patients to Sutene (Sunitinib, Pfizer).
Although the number of patients and the observation period are still limited, the research team estimated that Savolitinib had improved its effectiveness and safety than Sutene.
Keytruda surpassed Sutene by having combination therapy with Inlyta (Axitinib, Pfizer); the enemies and allies are mixed.
The results of the additional analysis of KEYNOTE-426 phase III in patients with advanced renal cell carcinoma who had first-line treatment were released.
According to the analysis of the 27-month median follow-up period, the overall survival rate at the 24-month was 74%, reducing the risk of death by 32% (HR=0.68) compared to the 66% of Sutene group.
Compared to 27% of the Sutene group, the 24-month PFS rate was 38%, which improved the risk of disease progression and death by 11% (HR=0.71).
The overall response rate was 20% higher than Sutene (60% vs 40%), and the median of the reaction duration was also longer than Sutene by 7.6 months (23.5 months vs 15.9 months),
These effects were consistent across all subgroups, such as IMDC risk and PD-L1 expression rates.
On the other hand, Opdivo showed an ORR of 29.3% with Opdivo monotherapy in HCRN GU16-260 clinical trials, which was conducted on patients with initial treatment for advanced renal cell carcinoma, suggesting a new alternative called Opdivo monotherapy besides Obdivo + Yervoy combination therapy.
On the contrary, Roche’s PD-L1 inhibitor Tecentriq(atezolizumab) failed to prove statistical differences in both disease-free survival and overall survival rate in the IMvigor010 phase III, which was conducted to confirm the effectiveness of post-operative adjuvant therapy in patients with high-risk muscle-invasive urothelial cell carcinoma.
Although the safety was consistent with previous studies, the research team explained that there were more cases of discontinuation of medication due to adverse effects than previous metastatic urothelial cell carcinoma studies.
◇ Prostate cancer – Parade the Presence of Takeda
In the prostate cancer field, GnRH antagonist Relumina (relugolix), which is being developed by Takeda, presented positive research results.
In the HERO phase III, which was conducted on 934 patients with androgen-sensitive advanced prostate cancer, the maintenance rate of castration of the first evaluation variable was 96.7% from the 29 days to 337 days, which was higher than 88.8% of the current hormone therapy Leuprolide. (p<0.0001)
In addition, the secondary evaluation variables, such as Testosterone inhibitor, PSA response rate, and FSH level, were all ahead of Leuprolide.
Furthermore, Relumina evaluated as a new standard therapy for lowering Testosterone in patients with advanced prostate cancerbecause the incidence rate of major cardiovascular events was 2.9%, which is lower than the Leuprolide group by 6.2%.
Moreover, the SWOG S1216 clinical trial, which compares cip17 inhibitor Orteronel and Bicalutamide which are developed by Takeda, confirmed the possibility of initial circulating tumor cells (CTC) as an indicator to predict PSA reactions in patients with metastatic castration-sensitive prostate cancer, and once again verified the effect of PSA-PFS on radioisotopes treatment Lutonium-177 PSMA-617 (LuPSMA) ANZUP protocol 16032 in phase II in comparison to Cabazitaxel.
◇ Ovarian cancer – Lynparza • KeytrudaMadeClinical Advance,MirvetuximabSoravtansineCounterattacks
In the ovarian cancer field, the antibody-drug conjugate Mirvetuximabsoravtansine recovered from the monotherapy, while thePRAP inhibitor Lynparza with lead and Keytruda released meaningful data.
First of all, Keytruda improved the overall response rate in both groups of 1% or more, and 10% or more of PD-L combined positive score (CPS) through the final report of the KEYNOTE-100 phase II study in patients with advanced recurrent ovarian cancer. The response lasted more than six months, and the median overall survival was 18.7 months, and it confirmed that the higher the PD-L1 CPS was, the longer it appeared.
Lynparza also proved the value of maintenance therapy in patients with BRCA positive platinum-sensitive ovarian cancer. In the SOLO-2 study, maintenance therapy has greatly extended the overall survival. (51.7 months vs 38.8 months, HR=0.74)
However, Lynparza left sorrow in combination therapy with Recentin (cediranib). In patients with high-grade platinum-sensitive ovarian cancer, the first evaluation variable, PFS was not improved compared to the standard chemotherapy.
On the other hand, in a phase 1/2 study conducted on patients with recurrent ovarian cancer, mirvetuximabsoravtansine, which had failed once in the ovarian cancer field, had an objective response rate of 43% in all patients and 61% in FRα expression patients with the combination therapy with Bevacizumab (product name Avastin, Roche).
In addition, Bavencio (avelumab, Merck • Pfizer) presented the possibility of cancer immunotherapy for the first time in patients with gestational trophoblastic tumor (GTT).
According to the research team, seven hCG were normalized during the 30-month median follow up at TROPHIMMUN phase II, and eight people, including one who was normalized after the cessation, and one of them was pregnant with a healthy condition.
◇ Head and neck cancer • Oral cancer – Oral Metronomic Chemotherapy, Alternatives to High-price Chemotherapy
Oral metronomic chemotherapy has been proposed as a new standard in head and neck cancer, where cancer immunotherapy and targeted therapies are considered as standard treatments.
As a result of the comparison between Cisplatin and oral metronomic chemotherapy, the researchers who conducted the Metro-CIS phase III study achieved significant improvement in overall survival, progression-free survival, and had low adverse effects.
In particular, the researchers argued based on KEYNOTE-048 and EXTREAM studies that the results of this study should be a new standard with a low-cost where the only expensive anticancer drugs such as Keytruda and Erbitux are placed in the National Comprehensive Cancer Network (NCCN) guidelines.
The researchers pointed out that the NCCN guidelines only offer high-priced anticancer drugs as a standard therapy, which made low-income countries challening to follow.
There are also noteworthy study results of Korean researchers on adenoid cystic carcinoma with the support of the adenoid cystic carcinoma research foundation.
In the absence of many related studies, Inlyta made significant improvements in PFS.
At 25.4 months of the median follow-up period, the six-month PFS was 73.2% in Inlyta group, which was higher than 23.3% of the observation group, and the median of the PFS was 10.8 months, far longer than 2.8 months of the observation group.
The disease control rate was also higher than the observation group by 48.1%, and the objective response rate was distinguished by 3.3% and 0%.
The KEYNOTE-048 study, which compared Keytruda and Keytruda + chemotherapy to Erbitux + chemotherapy in patients with metastatic head and neck squamous cell carcinoma, revealed an additional analysis of the effects of 2nd progression-free survival (PFS2) in recurrent patients.
Although the results of the study showed that the 2nd progression-free survival (PFS2) of Keytruda monotherapy or Keytruda+chemotherapy combination group was improved over the Erbitux group in both the PD-L1 combined positive score (CPS) and the patient group with 20 or higher, the PFS improvement was not confirmed in the entire patient record in Keytruda monotherapy group.
◇ Hematologic malignancy –Multiple Early Clinical Data
In the hematologic malignancy field, early clinical data such as phase I and II were focused.
Margrolimaband Azacitidine (product name Vidaza, BMS) reduced the transfusion dependence on more than 50% of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and increased the reaction rate.
Moreover, Enasidenib (product name Idhifa, BMS) and Azacitidine combined therapy had a higher complete remission rate and overall response rate than Azacitidine monotherapy in new diagnoses of IDH2 mutated acute myeloid leukemia.
On the other hand, Azacitidine and Pevonedistat combined therapy had similar safety in high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia (CMML), and low-level acute myeloid leukemia, but so meaningful improvement was made in myelosuppression rate, overall survival, and reaction rate.
In the ZUMA-5 phase II study in patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL), the CAR-t treatment, Yescarta (AxicabtageneCiloleucel, Gilead), recorded 94% of overall response rate at 11.5 months of an average follow-up, 79% of complete response, and overall, 68% of patients are maintaining the response with good condition.
Abbvie’s Venclexta (venetoclax) resulted in a 59% overall response rate and a 48% complete response in the CRC043 phase II study in Richter’s syndrome patients, with a median progression-free survival and overall survival of 16.3 months. The research team believes that this is a historically meaningful result.
Allogene’s CAR-t treatment ALLO-50 and ALLO-647 also showed potential for relapsed refractory large B-cell or follicular lymphoma in phase I of the ALPHA clinical trial.
Keytruda improved progression-free survival in a KEYNOTE-204 study, which compared Adcetris (Brentuximab, Takeda) in relapsed refractory non-Hodgkin’s lymphoma patients.
At 24.7-month of median follow-up, the median progression-free survival was 13.2 months, longer than the 8.3 months of the Adcetris group, and the risk of disease progression or death was reduced by 35% (HR=0.65, p=0.00271).
Researchers agreed that Keytruda should be a standard therapy in related indication since the rate of progression-free survival was 53.9% in Keytruda group and 35.6% in Adcetris group, 65.6% and 54.2% of objective response rate, and the median response duration was 20.7 months and 13.8 months for Keytruda group and Adcetris group.
In multiple myeloma, BMS’ CAR-t treatment, IdecabtageneVicluecel, showed response duration in KarMMA study of relapsed refractory patients.
At 11-month median follow-up, the overall response rate was 73%, the median progression-free survival was 8.6 months, the median response duration was 10.5 months, and the objective response rate in all subgroup analyses exceeded 50%.
In addition, Xpovio (Selinexor) of Karyopharm Therapeutics also improved its progression-free survival and objective response rate with Bortezomib + Dexamethasone (Vd) in Boston phase III, which was conducted on 402 patients with relapsed refractory multiple myeloma.
The median progression-free survival was 13.93 months, longer than 9.46 months of the Vd group (HR=0.70, p=0.0066), and the objective response rate was 76.4%, higher than 62.3% of the Vd group.
However, BMSEmpliciti (elotuzumab) tried to find out the potential in newly diagnosed multiple myeloma patients with lenalidomide, bortezomib, and dexamethasone (RVd) in SWOG-1211 phase II. Still, both the progression-free survival and the overall survival remained without improvement.
Besides, Beigene’sBrukinsa (zanubrutinib) challenged Waldenstrom Imbruvica (ibrutinib) and had a higher complete response and partial response but failed to acquire statistical significance.
◇ Lung cancer – Competition of Cancer Immunotherapy • TKI
Since lung cancer is the most reliable cash cow for cancer immunotherapy and targeted therapies, the research has been actively engaged.
ASCO20 invited Tagrisso (osimertinib, Astra Zeneca), the first EFGR-TKI to achieve a remarkable outcome in post-operative adjuvant therapy to the keynote speech, and Iressa (Gefitinib, Astra Zeneca) had found new values in patients with stages 2~3A (N1, N2) active EGFR.
After the resection, the disease-free survival rate was significantly improved than chemotherapy (3 years DFS 40.3% vs 33.2%). However, in the follow-up treatment, multiple patients used subsequent therapies, and the difference in overall survival rates was not found.
Nevertheless, the researchers said that the study had the best consequence among all reviews on complete resection of non-small cell lung cancer, after carrying out the overall survival (median value) of 75.5 months in Gefitinib.
The challenge against small cell lung cancer (SCLC) resulted in success, but it was not tidy.
In another study, Tagrisso and Iressa’s combination therapy was also highlighted. The research is expected that the combination of the two drugs will reduce resistance expression as Tagrisso functions on the T790M mutation of Iressa and Iressa on the C797S.
The researchers explained that the reaction rate had no difference from what Tagrisso had shown in the first treatment, and the plasma cleaning was quick because no active person was detected in 82.4% of patients at the time of 2-week treatment while the tolerability was not a problem.
MSD revealed the final analysis of the KEYNOTE-604 study, which was conducted to confirm the additional benefits of Keytruda for etoposide + cisplatin-based chemotherapy (EP) in patients with extensive small-cell lung cancer.
The meaningful improvement was made in the 2nd interim analysis with a relative risk of 0.75 during the progression-free survival, but in the final study, the relative risk improved to 0.80, with the improvement in median value from 10.8 months to 9.7 months, but failed to reserve the statistical significance.
However, the research team explained that the post-analysis showed that the relative risk of the overall survival was reduced to 0.78 and the p-value to 0.0124, resulting in statistical significance.
The overall response rate was 71% for Ketruda and 62% for placebo groups at the time of final analysis, while the median value for the response duration was 4.2 months for Ketruda and 3.7 months for placebo groups.
The researchers analyzed that the Keytruda + EP is the first-line treatment for patients with extensive non-small cell lung cancer, which significantly improves the progression-free survival and prolongs the overall survival compared to the placebo group + EP.
Meanwhile, Astra Zeneca also tried to improve the treatment results by adding Imfinzi and Tremelimumab with EP to extensive non-small cell lung cancer but failed to achieve the goal.
In the CASPIAN study, EP + Imfinzi combined therapy significantly improved the overall survival (HR=0.75, p=0.0032), but did not reach statistical significance in groups which included Tremelimumab.
On the contrary, in the phase II study of CCTG BR.34 in patients with metastatic stage 4 squamous or squamous non-small cell lung cancer, platinum-double chemotherapy was added to the Imfinzi + Tremelimumab, but the overall survival showed no improvement, and the toxicity was increased.
However, there were benefits in the objective response rate and progression-free survival, and especially in patients with a PD-L1 expression rate (TSP) of 50% or higher, the overall survival was improved.
Sanofi and Daiichi Sankyo challenged the non-small cell lung cancer field with the antibody-drug conjugate.
Sanofi conducted a study with 92 non-squamous non-small cell lung cancer patients who were expressed SAR408701 in carcinoembryonic antigen-related cell adhesion molecule 5and found out the possibility by checking the objective response rate of 7.1% in moderate-expression patients and 20.3% in patients with overexpression, and 17.8% in patients with previous PD-1 or PD-L1 inhibitor treatment experience.
Daiichi Sankyo also confirmed the possibility of T-DXd (DS-8201) in the phase II clinical trial of DESTINY-Lung01 for patients with HER2 mutated metastatic non-small cell lung cancer.
In this clinical trial, 45.2% of patients had brain metastasis, and most of them had previously been treated with platinum-based chemotherapy or PD-L1 or PD-L1 inhibitors and found out 90.5% disease control rate and the median progression-free survival of 14.0 month.
Roche doubled the objective response rate (31.3% vs 16.2%) and the median progression-free survival (5.4 months vs 3.6 months, HR=0.57) in the CITYSCAPE phase II study, which TIGIT antibody Tiragolumabwas added to Tecentriq in the first-line treatment of non-small cell lung cancer patients with PD-L1 expression.
However, in the NEJ026 phase III study, in which Avastin was added to Tarceva (erlotinib) for EGFR-positive non-squamous non-small cell lung cancer patients who did not have chemotherapy treatment, failed to obtain statistical significance as patients treated with Tagrisso in the second-line treatment were reflected.
BMS has made significant progress in non-small cell lung cancer through a combination therapy of Opdivo and Yervoy.
In CheckMate 9LA clinical trial, which aimed to compare the first-line treatment effects in recurrent non-small cell lung cancer patients, found a result that the 2nd cycle combination of Opdivo + Yervoy + platinum-based dual therapy has reduced the risk of death by 34% from the 4th cycle chemotherapy at 12.7 months of the median follow-up period (median overall survival 15.6 months vs. 10.9 months, HR= 0.66).
Furthermore, 38% of patients with a PD-L1 expression rate of more than 1% and 34% of patients with less than 1% survived until the third year of treatment.
Chinese researchers unveiled a SINDA phase II study that adds stereoradiography with EGFR-TKI in the first-line treatment of EGFR mutated non-small cell lung cancer patients.
As a result, patients who were treated with stereotactic radiotherapy compared to the TKI treated group, progression-free survival (20.2 months vs 12.5 months, HR=0.6188, p<0.001), and overall survival (20.5 months vs 17.4 months, HR=0.6824, p<0.001,) were improved.
◇ Melanoma – Focused on long-term • follow-up studies on cancer immunotherapy
In the melanoma field, where immuno-cancer drugs have confirmed the possibility for the first, long-term follow-up data, and follow-up studies have lined up.
EORTC 1325-MG/Keynote 054 phase III is a study comparing Ketyruda and placebo in patients with complete melanoma resection, and Keytruda’s 3-year recurrence-free survival (RFS) was 64%, higher than 44% of the placebo group (HR=0.56).
The research team explained that regardless of whether PD-L1 is expressed or not, the effect of improving the recurrence-free survival has been maintained continuously.
Although it is not cancer immunotherapy, the combination therapy of Ranfinlar (product name Dabrafenib) + Meqsel (Trametinib, Novartis) that mimics BRAF V600 mutations also revealed the results of COMBI-AD’s five-year follow-up.
This study, with resected stage III BRAF V600 mutant melanoma patients, compared to the placebo group, showed long-term effects with the recurrence-free survival at four years of 55% and 38%, and 52% and 36% at five years.
The studies have also been introduced to answer patients who have been treated with PD-1 or PD-L1 inhibitor monotherapy.
Since about two-thirds of metastatic melanoma patients develop resistance to PD-1 inhibitors, BMS compared Yervoy + Opdivo combination therapy as an alternative.
As a result, at 22.3 months of the median follow-up period, the response rate of the combined group was 31%, higher than 12% of the single group, and the progression-free survival and overall survival were also higher with 27% and 13%, and 57% and 38%. There was no difference between PD-1 expression or BRAF mutation.
In the same environment, there was also a study using Yervoy with Keytduda. As a result of maintaining Keytruda after using Keytruda and Yervoy in the initial four times, the response rate was 31%, the median progression-free survival was 4.7 months, and the progression-free survival at six months was 45%.
There were also attempts to reduce the use of Yervoy + Opdivo combination therapy, which required at least four doses. It is explained that evaluating the response through CT after two treatments in unresectable stage 3 and 4 melanoma patients will help to distinguish patients who are no longer responding.
Moreover, research on evaluating Yervoy + Opdivo combination therapy as an adjuvant therapy before surgery, astudy that combines mucosal melanoma with Tuoyi (toripalimab, Junshi Bio) and Inlyta, and research on simultaneous injection of Opdivo into lumbar spine and vein to metastatic melanoma with leukemia also showed possibilities.
◇ Childhood cancer – Attention to various attempts using TKI
TKI’s remarkable performances dominated in the childhood cancer field.
In ALK-induced neuroblastoma, Zykadia (ceritinib, Novartis) and Lobrena (lorlatinib, Pfizer) showed possibilities followed by Stivarga (regorafenib, Bayer) in childhood solid cancer including rhabdomyosarcoma, and Rafinlar + Meqsel combination therapy in low-grade glioblastoma.
To improve the reaction rate of MIBG (131-metaiodobenzylguanidine) injections in neuroblastoma, MIBG alone, and MIBG + Vincristine + Irinotecan were used.In a study that evaluated the combination therapy of MIBG and Vorinostat (product name Zolinza, MSD), the response rate was highest in the combination therapy with Vorinostat, and in both Irinotecan and Vincristine showed no improvement in response rate while only the toxicity increased.
Although the AOST1421 clinical results, which added Unituxin (Dinutuximab, United Therapeutics) with GM-CSF in recurrent osteosarcoma patients, were released, the primary goal of disease control rate (the proportion of patients who did not have an issue until 12 months after recruitment, set to 40%) of 30.7% did not reach the goal.
CAR-t treatment CTL019/CTL119 (Novartis), which targets CD19, disclosed possibility in B-cell acute lymphoblastic leukemia with brain metastasis, and Torisel (Temsirolimus, Pfizer) also showed potential in relapsed or refractory acute lymphoblastic leukemia.
Studies related to the prognosis of childhood cancer patients have also been published, and the combination therapy of Dexrazoxane and Doxorubicin in childhood cancer survivors has better left ventricle (LV) contractile function and less regional wall stress than Doxorubicin monotherapy.
In addition, a study has been released that B-cell acute lymphoblastic leukemia patients with down syndrome need to approach less toxic targeted treatments and immunotherapy because of poorer prognosis, such as recurrence or drug toxicity, than those without down syndrome.
◇ Sarcoma – Glivec, the first targeted treatment, announced 10-year follow up results at GIST
In the field of sarcoma, studies related to Ewing sarcoma have been mainly discussed, and GIST has released a study comparing the recurrence-free survival of Glivec (Imatinib, Novartis) as a post-operative adjuvant therapy.
This study, which has an average follow-up period of 119 months, compared the group that tookGlivec for one year as a post-operative adjuvant therapy with the group that took it for three years.
As a result, the 5-year recurrence-free survival of the group, which used Glivec for three years was 71.4%, and the 10-year recurrence-free survival was 52.5%, and they were higher than 53.0% and 41.8% of the one year administered group.
It can be explained that if Glivec is administered for three years after surgery, half of the patients can avoid death compared to the patients who took it for a year after ten years.
The research about the combination therapy of MEK inhibitor Mektovi and Glivec at GIST also showed 68.4% of objective response, which can be said as 8 out of 9 patients were able to resect after the treatment.
Various attempts have been made in the Ewing sarcoma field.
First of all, in Ewing 2008R3 (Eudra) clinical trials for high-risk Ewing sarcoma patients, Treosulfan and Melphalan were added to high-dose chemotherapy after autologous hematopoietic stem cell re-injection but did not achieve clinical benefits. However, there is a possibility for children under the age of 14.
In Ewing sarcoma, a study comparing European treatments (Regimen) with American treatments is also interesting.
According to the researchers, European treatment is Vincristine + Ifosfamide + Doxorubicin + Etoposide (VIDE) induction therapy after Vincristine + Actinomycin D + Ifosfamide (VAI) or Vincristine + Actinomycin D + Cyclophosphamide consolidation therapy.
The American treatment is Vincristine + Doxorubicin + Cyclophosphamide (VDC) / Ifosfamide + Etoposide (IE) induction therapy after IE / Vincristine + Cyclophosphamide (VC) consolidation therapy.
Comparting this, the researchers explained that during the 1.7-month median follow-up period, U.S. treatments benefited from both pre-defined factors, as well as the event-free survival compared to European therapies.
In the AIEOP EW-2 study, which added 180days of celecoxib to cyclophosphamide in patients with metastatic Ewing sarcoma, positive results were presented in multiple metastatic sarcomas.However, the researchers noted that more follow-up is needed in pulmonary metastases patients.
In the ISG/AIEOP EW-2 study, in which the initial combination treatments of Temodal (Temozolomide, MSD) and Irinotecan were used twice in the first multifocal Ewing sarcoma patients, the response rate was 59%, the ECOG/Lansky score improved by 73.5%, and the pain was reduced or eliminated in 91% of patients.
LMS-02 phase II, which improved in progression-free survival and overall survival when combining Doxoribicin and Yondelis (Trabectedin, Janssen) with recurrent/metastatic uterine cancer or soft tissue leiomyosarcoma patients, and LEADER 1b/ phase II study, which showed a possibility of Lenvima and Halaven (Eribulin, Eisai) combination therapy to progressive liposarcoma and leiomyosarcoma, were introduced.
Moreover, in a study combining Opdivo and Yervoy as an adjuvant therapy before the radiation in undifferentiated pleural sarcoma and multilateral lipoma, which cannot be surgically resected, showed significant changes in pathology or tumor size in patients with undifferentiated pleural sarcoma.The researchers believe these results are more positive than what other studies have confirmed in the past.
In JCOG1306 phase II / III clinical trials, which compared Adriamycin and Ifosfamide combination therapy and Gemcitabine and Docetaxel combination therapy in high-grade soft tissue sarcoma, failed to prove its non-inferiority in Gemcitabine and Docetaxel combination therapy while it had less toxic.
◇ Palliative care – To the last moment of your life with beauty
Meanwhile, at the end of ASCO20, there were not only the prognosis of patients but also suggestions to spend the end of life less painfully and beautifully.
Among the study to reduce patients’ pain directly, Armodafinil drug showed possibility in glioblastoma patients to improve fatigue.Still, after more than four weeks of actual radiation treatment, there were reports that the drug failed to identify significant differences compared to placebo groups.
In another research showed that palliative care, which combines mitigating and tumor management for patients with acute myeloid leukemia, improves the quality of life for patients who have to endure aggressive treatment at the end, reduces psychological pain, and decreases their chances of receiving chemotherapy, compared to treatment that only manages tumors.
In addition, studies using tetrahydrocannabinol (THC) and cannabidiol (CBD) to improve vomiting in patients undergoing chemotherapy and acupuncture to reduce pain were introduced.
THC/CBD, although it reduces vomiting, had higher rates of adverse reactions, such as sedation, dizziness, loss of direction, nausea, and use of emergency drugs, patients preferred THC/CBD.
A study showed that acupuncture improved cancerous pain symptoms for ten weeks by giving examples of patients with chronic pain caused by cancer, electrical or ear acupuncture were effective in relieving pain, and peripheral neuropathy caused by anti-cancer drugs had less pain in groups that added acupuncture than standard therapy.
Along with the strategy of using Haloperidol and chlorpromazine to reduce the common symptom, delirium, in terminal cancer patients, studies have also shown that yoga or cognitive behavior therapy (CBT-I) is more crucial than health education for cancer survivors.